Author: Ravi Shankar

Single-dose miv-cel continues to demonstrate promising clinical benefit in progressive multiple sclerosis, achieving robust CAR T-cell penetration in the central nervous system (CNS) and improving disability scores while removing the need for chronic immunotherapies

Durable results extending beyond two years in the first patient treated

Consistent, well-tolerated safety profile with no high-grade CRS and no cases of ICANS or IEC-HS

RMAT designation granted in treatment of non-active secondary progressive multiple sclerosis (naSPMS); update on development strategy expected by early 2027

EMERYVILLE, Calif., Oct. 23, 2026 (GLOBE NEWSWIRE) — Kyverna Therapeutics, Inc. (Nasdaq: KYTX), a late-stage clinical immunology company pioneering transformative therapies for people with neurologic autoimmune diseases, today announced updated data from a Phase 1 investigator-initiated trial (IIT) of miv-cel (mivocabtagene autoleucel, KYV-101) in patients with progressive multiple sclerosis (PMS). The data will be shared today in an oral presentation at MS Toronto 2026, the joint ACTRIMS-ECTRIMS meeting.

“There remains a substantial unmet need for therapies that can meaningfully alter the course of progressive multiple sclerosis,” said Jeffrey Dunn, MD, Lily Sarafan Director of Neuroimmunology, Clinical Professor and Chief of Neuroimmunology at Stanford University. “In this early-phase study, miv-cel demonstrated encouraging tolerability, with evidence of CAR T-cell penetration into the central nervous system and biologic findings consistent with an immune reset. Importantly, we also observed sustained improvements in measures of neurologic disability and patient-reported function among evaluable participants. While these preliminary findings require confirmation in larger controlled trials, they provide an important proof of concept that miv-cel may offer a potential novel approach to treating progressive multiple sclerosis.”

Stanford Oral Presentation
Title: Safety and Preliminary Efficacy of CD-19 Directed CAR T-Cell Therapy in Progressive Multiple Sclerosis: A Phase 1 Study
Presenter: Jeff Dunn, M.D., Lily Sarafan Director of Neuroimmunology, Clinical Professor and Chief of Neuroimmunology, Stanford University
Date & Time: Friday, October 23, 2026, 11:05 – 11:15 AM ET

Stanford University is conducting an open-label, Phase 1, single-center study of miv-cel in patients with non-relapsing progressive multiple sclerosis, either secondary progressive MS (SPMS) or primary progressive MS (PPMS). Six patients were treated with either 33M (n=3) or 100M (n=3) CAR T-cell dose levels using a bendamustine lymphodepleting (LD) regimen.

The oral presentation features updated data from six patients with available efficacy data from five patients, with follow-up of more than two years in the longest-treated patient. Key highlights include:

Efficacy:

• All five patients with available data demonstrated stable to improved expanded disability status scale scores (EDSS) as of last follow-up, with the majority (4/5) showing sustained clinical benefit through one year.
• Four patients with more than one-year of follow-up sustained improvement without further need for chronic immunotherapies. The first patient treated with miv-cel achieved sustained clinical benefit beyond two years.

Biological activity:

• Robust CAR T-cell expansion detected in peripheral blood and penetration in cerebrospinal fluid (CSF), with peak levels at approximately day 14.
• Complete depletion of CD19-positive peripheral B cells was achieved in all participants, followed by repopulation beginning at month 3, consistent with the emergence of naïve B cells, supporting evidence of immune reset.
• Additional biomarker data, including CSF oligoclonal bands and kappa free light chain, continue to support favorable immunological impact at one year.

Safety:

• Consistent, well-tolerated safety profile with no high-grade CRS and no reported cases of ICANS or IEC-HS.

“We are encouraged by the long-term durability and safety results with miv-cel in progressive multiple sclerosis, which add to the strong body of evidence supporting miv-cel’s transformative potential across neurologic autoimmune diseases,” said Naji Gehchan, Chief Medical and Development Officer of Kyverna Therapeutics. “The consistent, durable clinical benefit and well-tolerated safety profile observed across our indications are underpinned by miv-cel’s unique construct, specifically developed by Kyverna in autoimmune disease to enable immune reset by deeply and broadly depleting B-cells with a single dose. With our RMAT designation, we look forward to working with the FDA on our development plan in progressive multiple sclerosis and providing an update by early 2027.”

About miv-cel (mivocabtagene autoleucel, KYV-101)
Miv-cel is a fully human, autologous, CD19-targeting CAR T-cell therapy with CD28 co-stimulation. It is uniquely designed for potency and tolerability with the potential to achieve deep B-cell depletion, reset the immune system, and deliver durable drug-free, disease-free remission in autoimmune diseases with a single dose. Miv-cel is under investigation for B-cell driven autoimmune diseases and is produced using a well-established, validated manufacturing process. To date, more than 100 patients have been treated with miv-cel across a range of autoimmune diseases, and the clinical data demonstrates a consistent and well-tolerated safety profile.

About Multiple Sclerosis
Multiple sclerosis is a chronic autoimmune disease causing neurodegeneration, in which patients can experience a range of symptoms including blurred vision, slurred speech, tremors, numbness, extreme fatigue, problems with memory and concentration, and, in severe cases, the inability to walk or stand, B cells play a significant role in MS by producing autoantibodies that attack the protective sheath around the nerves, activating T cells, and increasing inflammation. Current disease-modifying treatments for MS aim to reduce the frequence of disease relapse and delay a progression of disability, but the disease remains a chronic condition that will progressively worsen for most patients.

About Kyverna Therapeutics
Kyverna Therapeutics, Inc. (Nasdaq: KYTX) is a late-stage clinical immunology company pioneering differentiated therapies with curative potential for neurologic autoimmune diseases. Kyverna’s lead autologous CD19-targeting CAR T-cell therapy candidate, miv-cel (mivocabtagene autoleucel, KYV-101), has demonstrated the potential to fundamentally change the treatment paradigm across multiple B-cell-driven autoimmune diseases. Kyverna is advancing its potentially first-in-class neuroimmunology franchise with its recently completed registrational trial in stiff person syndrome (SPS) and an ongoing registrational trial for generalized myasthenia gravis (gMG).

Miv-cel has received three FDA Regenerative Medicine Advanced Therapy (RMAT) designations, in SPS, gMG, and non-active secondary progressive multiple sclerosis (naSPMS) based on compelling clinical data and significant unmet need, further reinforcing the therapy’s potential across neuroimmunology. Additionally, the Company continues to advance new innovations that broaden access and choice for patients, expanding its leadership position in the field. For more information, please visit https://kyvernatx.com.

Forward-Looking Statements
Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute “forward-looking statements.” The words, without limitation, “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these or similar identifying words. Forward-looking statements in this press release include, without limitation, those related to: miv-cel’s potential to meaningfully alter the course of, or offer a novel approach to treating, progressive multiple sclerosis; miv-cel’s transformative potential across neurologic autoimmune diseases; Kyverna’s development plans in progressive multiple sclerosis and expected timing for providing an update on its development strategy for multiple sclerosis; the potential for miv-cel to achieve deep B-cell depletion, reset the immune system, and deliver durable drug-free, disease-free remission in autoimmune diseases with a single dose or to fundamentally change the treatment paradigm across multiple B-cell-driven autoimmune diseases; Kyverna’s pipeline opportunities; and Kyverna’s potentially first-in-class neuroimmunology franchise. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: uncertainties related to market conditions; risks related to the timing and outcome of regulatory submissions and interactions with the FDA; the ability to enroll patients in clinical trials on anticipated timelines; the possibility that topline results may change following further analysis or differ from final results; the possibility that results from prior clinical trials, named-patient access activities and preclinical studies may not necessarily be predictive of future results; and other factors discussed in the “Risk Factors” section of Kyverna’s most recent Annual Report on Form 10-K and Quarterly Reports on Form 10-Q that Kyverna has filed or may subsequently file with the U.S. Securities and Exchange Commission. Any forward-looking statements contained in this press release are based on the current expectations of Kyverna’s management team and speak only as of the date hereof, and Kyverna specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise.

Contact:
Investors: InvestorRelations@kyvernatx.com
Media: media@kyvernatx.com

• Of the 106 peptide and nanobody drug conjugates in active development, roughly 63% are still preclinical, which places many of the decisions that shape manufacturability in the design phase.
• Cyclization, lipidation, chelator installation and payload conjugation each add process and analytical requirements that are best addressed while the molecule can still be changed
• WuXi AppTec carries those design decisions through building-block supply, analytical development and manufacturing within one global quality system.

San Diego, CA, Oct. 23, 2026 (GLOBE NEWSWIRE) — There are about 106 peptide and nanobody drug conjugates in active development, and around 63% of them are still preclinical, according to a 2026 Citeline analysis of Pharmaprojects data.¹ For most of those programs, including the peptide conjugates among them, the structural choices that decide whether the molecule can be made at scale are not yet locked, which makes design the stage that shapes much of peptide conjugate development. Each added element, whether a lipid, a chelator or a payload, brings its own chemistry, impurities and analytical demands. After nomination, a change to the sequence, the modification site or the conjugation strategy can send the program back through characterization and biological testing. 

WuXi AppTec, a contract research, development and manufacturing organization (CRDMO), works as a trusted partner to biotech and pharmaceutical innovators across more than 30 countries. For peptide conjugate programs, five decisions made before nomination shape whether the molecule can be manufactured at scale.

Map Each Structural Modification to Its CMC Consequence

The first decision is to write down what each modification adds to the chemistry, manufacturing and controls (CMC) package, because the consequences are specific and, for the most part, foreseeable.

Modification	What it adds to the process	What it adds to the analytics
Macrocyclization	Ring-closing chemistry; residual-catalyst control when metal-catalyzed	Resolution of ring-size and linkage variants
Lipidation	Greater hydrophobicity; altered solubility and aggregation; different purification behavior	Methods that track self-association and aggregation
Chelator installation	Sensitivity to trace metals from solvents, reagents and containers; a metal budget	Separation of species that differ only in the metal occupying the chelate
Payload conjugation	Containment for potent payloads; linker-stability control	Assignment of conjugation products and free-payload impurities

Secure Specialized Building-Block Routes Before the Candidate Depends on Them

Conjugates draw on nonstandard components, including unnatural amino acids, linkers and chelators, that are often available only in research quantities or from one supplier. For each of them, the decision before nomination is whether a scalable, reproducible route exists or has to be built alongside the peptide. A component found to be single-source after nomination leaves two options: either a long wait or a redesign that reopens biology.

Develop Analytical Methods That Resolve Closely Related Species

Conjugation produces species that resemble the product, including sequence variants and under-reacted and over-reacted conjugation products. Where a chelator is present, the process can also form complexes with adventitious metals that co-elute with the product and resist assignment by mass alone. Methods are ready only when they can separate and assign every species the construct is expected to generate. Running method development alongside route development surfaces any co-eluting species the method cannot resolve while the team can still adjust the chemistry.

Set the Control Strategy Around the Individual Construct

A control strategy written for a linear peptide will not carry over unchanged to its lipidated, cyclized or chelator-bearing analog. For chelator-containing molecules in particular, the choice of solvents, the sequence of process steps and the materials that touch the product are all fixed against a limit on allowable trace metals, decided at the start of process development rather than discovered at release.

Carry Design Decisions Through One Global Quality System to Clinical Supply

The value of making these decisions early depends on keeping them intact as the program advances. WuXi TIDES, the peptide and oligonucleotide platform of WuXi AppTec, connects discovery synthesis, unnatural amino acid and linker supply, conjugation chemistry, analytical development and manufacturing within one CRDMO platform and one global quality system, so the metal budget, the method and the supply route chosen during optimization are designed to carry through to development and commercial supply.

“By connecting chemistry development, manufacturing, and supply within a unified system, teams can operate in parallel, anticipate challenges, and maintain consistent quality across regions,” said Yu Lu, Senior Vice President of WuXi TIDES, part of WuXi AppTec.

In a published case study, WuXi AppTec reported supporting a cyclic peptide-based radionuclide conjugate program by developing an in-house route for a critical unnatural amino acid and coordinating discovery, testing, process development and impurity control. Analytical and purification teams developed methods to distinguish metal-containing species, while process and formulation teams evaluated solvents, operating conditions and contact materials to limit metal contamination. Overall yield rose from 29% to 44%, and a telescoped synthesis process reduced the synthesis cycle and material use by approximately 30% each. Outcomes depend on the individual program.

Frequently Asked Questions

Question: What are peptide conjugates, and why are they used?

Answer: Peptide conjugates attach another component to a peptide to add a function. A drug payload can enable targeted delivery, a fatty-acid moiety can prolong circulation through albumin binding, and a chelator can carry a radionuclide for imaging or therapy, as lutetium-177 dotatate does for somatostatin receptor-positive neuroendocrine tumors. Peptide-drug conjugates face a particular constraint: peptides clear quickly, so the construct has to reach its target and release its payload within a short window.

Question: What makes peptide conjugates harder to develop than linear peptides?

Answer: Each added element brings chemistry beyond standard chain assembly, along with its own impurities and analytical requirements. A linker, a lipid, a chelator or a payload changes how the molecule behaves in purification, how it aggregates, which species the analytical method must separate and, for potent payloads, how the process must be contained. None of these is unmanageable, but each has to be designed for, which is why conjugate programs benefit from process and analytical input during optimization rather than after nomination.

Question: Why do trace metals matter in chelator-containing peptide conjugates?

Answer: A chelator such as DOTA, built to hold a therapeutic radionuclide, will also pick up metals that leach from solvents, reagents and container surfaces. Those metals occupy chelation sites and can reduce the efficiency of later radiolabeling. The resulting complexes look like the product on the column and can be hard to assign by mass alone, so they are easy to miss and hard to remove. Controlling them means setting a trace-metal limit at the start of process development, choosing solvents, step order and contact materials against that limit, and using an analytical method that can tell apart species that differ only in the metal held in the chelate.

Question: How do potent payloads change peptide conjugate manufacturing?

Answer: They add containment and impurity-control requirements that a plain peptide process does not carry. A highly potent payload has to be handled in facilities and equipment designed to protect operators and prevent cross-contamination, and the analytical package has to track free payload and payload-related impurities alongside the peptide species. Linker stability becomes a process parameter as well as a pharmacology one, because premature release during synthesis, purification or storage shows up as an impurity. Those requirements are easier to meet when the payload and linker are chosen with the manufacturing route in view.

Question: How does lipidation affect peptide purification and formulation?

Answer: A fatty-acid chain added to extend half-life makes the molecule more hydrophobic and more prone to self-association. In purification that can shift retention, lower recovery and complicate separation from related species. In formulation it can limit achievable concentration, affect stability and narrow the choice of dosage form. Evaluating those effects when the lipidation site and linker are chosen lets the team select the variant that extends exposure without creating a purification or formulation problem later.

Source: 

¹ Citeline, “Peptide and nanobody drug conjugates pipeline takes shape,” June 2026, based on Pharmaprojects data current to January 2026.

About WuXi AppTec

WuXi AppTec is a trusted partner and contributor to the pharmaceutical and life sciences industries, providing R&D and manufacturing services that help advance healthcare innovation. With operations across Asia, Europe, and North America, we offer integrated, end-to-end services through our unique CRDMO (Contract Research, Development, and Manufacturing Organization) platform. We are privileged to work alongside partners across 30+ countries, supporting their efforts to bring breakthrough treatments to patients. Guided by our vision that every drug can be made, and every disease can be treated, we are committed to advancing breakthroughs for patients—one collaboration at a time. Learn more at https://www.wuxiapptec.com.

CONTACT: Majed Soufi
Zen Media
PR@zenmedia.com

LISLE, Ill., Oct. 23, 2026 (GLOBE NEWSWIRE) — CTS Corporation (NYSE: CTS) today announced that it has completed the acquisition of Millar Holdings, Inc. (“Millar”) for $50 million, net of cash acquired and debt assumed, with additional contingent consideration payable subject to the achievement of specified financial performance targets. Millar specializes in the design, development, and manufacturing of advanced pressure sensing technologies for medical devices, life sciences, and industrial applications. The acquisition strengthens CTS’s position in advanced sensing technologies and expands its presence in diversified end markets.

“We are excited to welcome the Millar team to CTS,” said Pratik Trivedi, President and Chief Executive Officer of CTS Corporation. “Millar represents a highly strategic addition to our portfolio, expanding our presence in medical sensing while adding differentiated technology, talented employees, and strong customer relationships. We believe the combination will enhance our ability to deliver innovative sensing solutions to customers worldwide and create long-term value for our shareholders.”

Tim Daugherty, Chief Executive Officer of Millar, added, “Joining CTS marks an exciting new chapter for Millar and an incredible opportunity to build on everything our team has accomplished over the past 55-plus years. We’ve always been passionate about pushing the boundaries of sensor technology and helping our customers bring innovative solutions to life. With CTS’s global reach, complementary technologies, and engineering expertise, we’re positioned to accelerate innovation, expand our capabilities, and create even greater value for the customers and markets we serve.”

About CTS Corporation

CTS is a leading designer and manufacturer of products that Sense, Connect, and Move. The Company manufactures sensors, connectivity components, and actuators for applications in the aerospace and defense, industrial, medical, and transportation markets. CTS reported sales of approximately $564 million for the twelve months ended June 30, 2026. More information is available at www.ctscorp.com.

Investor Contact:
Ashish Agrawal
Vice President and Chief Financial Officer
CTS Corporation
4925 Indiana Avenue

Lisle, IL 60532 USA
+1 (630) 577-8800
ashish.agrawal@ctscorp.com

Forward-Looking Statements

This press release contains forward-looking statements regarding anticipated benefits of the acquisition, future growth opportunities, and expected business performance. Actual results may differ materially from those expressed or implied by such statements due to various risks and uncertainties. CTS undertakes no obligation to update any forward-looking statements except as required by law.

TORONTO, Oct. 23, 2026 (GLOBE NEWSWIRE) — Middlefield Global Infrastructure Dividend ETF (TSX: MINF) (the “Fund”) is pleased to announce that distributions for the fourth quarter of 2026 will be payable to unitholders of Middlefield Global Infrastructure Dividend ETF as follows:

Record Date	Payable Date	Distribution Per Trust Unit
October 31, 2026	November 13, 2026	$0.04167
November 30, 2026	December 15, 2026	$0.04167
December 31, 2026	January 15, 2027	$0.04167

The trust units trade on the Toronto Stock Exchange under the symbol MINF.

The Fund offers a distribution reinvestment plan (“DRIP”) for unitholders which provides unitholders with the ability to automatically reinvest distributions, commission free, and realize the benefits of compound growth. Unitholders can enroll in the DRIP program by contacting their investment advisor.

About Middlefield

Founded in 1979, Middlefield is an independent, income-focused asset manager with offices in Toronto, Canada and London, England. For more than four decades, we have helped investors generate income and build wealth through active management and disciplined risk management. Today, Middlefield offers a growing range of investment strategies across global fixed income and equities, delivered through Canadian and European exchange-traded funds, mutual funds and alternative investment solutions for individual and institutional investors. Supported by an experienced investment team and a culture of independent thinking, Middlefield seeks to deliver attractive risk-adjusted returns, sustainable income and long-term capital appreciation across market cycles.

For further information, please visit our website at www.middlefield.com or contact our Sales and Marketing Department at 1.888.890.1868.

This press release contains forward-looking information. The forward-looking information contained in this press release is based on historical information concerning distributions and dividends paid on the securities of issuers historically included in the portfolio of the Fund. Actual future results, including the amount of distributions paid by the Fund, may differ from the monthly distribution amount. Specifically, the income from which distributions are paid may vary significantly due to: changes in portfolio composition; changes in distributions and dividends paid by issuers of securities included in the Fund’s portfolio from time to time; there being no assurance that those issuers will pay distributions or dividends on their securities; the declaration of distributions and dividends by issuers of securities included in the portfolio will generally depend upon various factors, including the financial condition of each issuer and general economic and stock market conditions; the level of borrowing by the Fund; and the uncertainty of realizing capital gains.  The risks, uncertainties and other factors that could influence actual results are described under “Risk Factors” in the Fund’s prospectus and other documents filed by the Fund with the Canadian securities regulatory authorities. The forward-looking information contained in this press release constitutes the Fund’s current estimate, as of the date of this press release, with respect to the matters covered hereby. Investors and others should not assume that any forward-looking statement contained in this press release represents the Fund’s estimate as of any date other than the date of this press release.

FORM 8.3

PUBLIC OPENING POSITION DISCLOSURE/DEALING DISCLOSURE BY
A PERSON WITH INTERESTS IN RELEVANT SECURITIES REPRESENTING 1% OR MORE
Rule 8.3 of the Takeover Code (the “Code”)

1.        KEY INFORMATION

(a)   Full name of discloser:	Davidson Kempner Capital Management LP
(b)   Owner or controller of interests and short positions disclosed, if different from 1(a):         The naming of nominee or vehicle companies is insufficient. For a trust, the trustee(s), settlor and beneficiaries must be named.
(c)   Name of offeror/offeree in relation to whose relevant securities this form relates:         Use a separate form for each offeror/offeree	easyJet plc
(d)   If an exempt fund manager connected with an offeror/offeree, state this and specify identity of offeror/offeree:
(e)   Date position held/dealing undertaken:         For an opening position disclosure, state the latest practicable date prior to the disclosure	22/10/2026
(f)   In addition to the company in 1(c) above, is the discloser making disclosures in respect of any other party to the offer?         If it is a cash offer or possible cash offer, state “N/A”	No

2.        POSITIONS OF THE PERSON MAKING THE DISCLOSURE

If there are positions or rights to subscribe to disclose in more than one class of relevant securities of the offeror or offeree named in 1(c), copy table 2(a) or (b) (as appropriate) for each additional class of relevant security.

(a)      Interests and short positions in the relevant securities of the offeror or offeree to which the disclosure relates following the dealing (if any)

Class of relevant security:	27 2/7p ordinary (ISIN-GB00B7KR2P84)
	Interests		Short positions
	Number	%	Number	%
(1)   Relevant securities owned and/or controlled:
(2)   Cash-settled derivatives:	20,333,951	2.68%
(3)   Stock-settled derivatives (including options) and agreements to purchase/sell:
TOTAL:	20,333,951	2.68%

All interests and all short positions should be disclosed.

Details of any open stock-settled derivative positions (including traded options), or agreements to purchase or sell relevant securities, should be given on a Supplemental Form 8 (Open Positions).

(b)      Rights to subscribe for new securities (including directors’ and other employee options)

Class of relevant security in relation to which subscription right exists:
Details, including nature of the rights concerned and relevant percentages:

3.        DEALINGS (IF ANY) BY THE PERSON MAKING THE DISCLOSURE

Where there have been dealings in more than one class of relevant securities of the offeror or offeree named in 1(c), copy table 3(a), (b), (c) or (d) (as appropriate) for each additional class of relevant security dealt in.

The currency of all prices and other monetary amounts should be stated.

(a)        Purchases and sales

Class of relevant security

Purchase/sale

Number of securities

Price per unit

(b)        Cash-settled derivative transactions

Class of relevant security	Product description e.g. CFD	Nature of dealing e.g. opening/closing a long/short position, increasing/reducing a long/short position	Number of reference securities	Price per unit
27 2/7p ordinary	CFD	Increasing a long position	228,146	GBP 6.7950

        
(c)        Stock-settled derivative transactions (including options)

(i)        Writing, selling, purchasing or varying

Class of relevant security

Product description e.g. call option

Writing, purchasing, selling, varying etc.

Number of securities to which option relates

Exercise price per unit

Type e.g. American, European etc.

Expiry date

Option money paid/ received per unit

(ii)        Exercise

Class of relevant security

Product description e.g. call option

Exercising/ exercised against

Number of securities

Exercise price per unit

(d)        Other dealings (including subscribing for new securities)

Class of relevant security

Nature of dealing e.g. subscription, conversion

Details

Price per unit (if applicable)

4.        OTHER INFORMATION

(a)        Indemnity and other dealing arrangements

Details of any indemnity or option arrangement, or any agreement or understanding, formal or informal, relating to relevant securities which may be an inducement to deal or refrain from dealing entered into by the person making the disclosure and any party to the offer or any person acting in concert with a party to the offer: Irrevocable commitments and letters of intent should not be included. If there are no such agreements, arrangements or understandings, state “none”

None

(b)        Agreements, arrangements or understandings relating to options or derivatives

Details of any agreement, arrangement or understanding, formal or informal, between the person making the disclosure and any other person relating to: (i)   the voting rights of any relevant securities under any option; or (ii)   the voting rights or future acquisition or disposal of any relevant securities to which any derivative is referenced: If there are no such agreements, arrangements or understandings, state “none”

None

(c)        Attachments

Is a Supplemental Form 8 (Open Positions) attached?

NO

Date of disclosure:	23/10/2026
Contact name:	Alex McMillan
Telephone number:	646 282 5805

Public disclosures under Rule 8 of the Code must be made to a Regulatory Information Service.

The Panel’s Market Surveillance Unit is available for consultation in relation to the Code’s disclosure requirements on +44 (0)20 7638 0129.

The Code can be viewed on the Panel’s website at www.thetakeoverpanel.org.uk.

TORONTO, Oct. 23, 2026 (GLOBE NEWSWIRE) — Middlefield Healthcare Dividend ETF (TSX: MHCD) (the “Fund”) is pleased to announce that distributions for the fourth quarter of 2026 will be payable to unitholders of Middlefield Healthcare Dividend ETF as follows:

Record Date	Payable Date	Distribution Per Trust Unit
October 31, 2026	November 13, 2026	$0.05
November 30, 2026	December 15, 2026	$0.05
December 31, 2026	January 15, 2027	$0.05

The trust units trade on the Toronto Stock Exchange under the symbol MHCD.

The Fund offers a distribution reinvestment plan (“DRIP”) for unitholders which provides unitholders with the ability to automatically reinvest distributions, commission free, and realize the benefits of compound growth. Unitholders can enroll in the DRIP program by contacting their investment advisor.

About Middlefield

Founded in 1979, Middlefield is an independent, income-focused asset manager with offices in Toronto, Canada and London, England. For more than four decades, we have helped investors generate income and build wealth through active management and disciplined risk management. Today, Middlefield offers a growing range of investment strategies across global fixed income and equities, delivered through Canadian and European exchange-traded funds, mutual funds and alternative investment solutions for individual and institutional investors. Supported by an experienced investment team and a culture of independent thinking, Middlefield seeks to deliver attractive risk-adjusted returns, sustainable income and long-term capital appreciation across market cycles.

For further information, please visit our website at www.middlefield.com or contact our Sales and Marketing Department at 1.888.890.1868.

This press release contains forward-looking information. The forward-looking information contained in this press release is based on historical information concerning distributions and dividends paid on the securities of issuers historically included in the portfolio of the Fund. Actual future results, including the amount of distributions paid by the Fund, may differ from the monthly distribution amount. Specifically, the income from which distributions are paid may vary significantly due to: changes in portfolio composition; changes in distributions and dividends paid by issuers of securities included in the Fund’s portfolio from time to time; there being no assurance that those issuers will pay distributions or dividends on their securities; the declaration of distributions and dividends by issuers of securities included in the portfolio will generally depend upon various factors, including the financial condition of each issuer and general economic and stock market conditions; the level of borrowing by the Fund; and the uncertainty of realizing capital gains.  The risks, uncertainties and other factors that could influence actual results are described under “Risk Factors” in the Fund’s prospectus and other documents filed by the Fund with the Canadian securities regulatory authorities. The forward-looking information contained in this press release constitutes the Fund’s current estimate, as of the date of this press release, with respect to the matters covered hereby. Investors and others should not assume that any forward-looking statement contained in this press release represents the Fund’s estimate as of any date other than the date of this press release.

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OR FOR DISSEMINATION IN THE UNITED STATES

TORONTO, Oct. 23, 2026 (GLOBE NEWSWIRE) — Hercules Metals Corp. (TSXV: BIG) (OTCQB: BADEF) (“Hercules” or the “Company“) is pleased to announce that as a result of strong investor demand, the Company has amended its agreement with Canaccord Genuity Corp. and BMO Capital Markets, as joint bookrunners, on behalf of a syndicate of underwriters (collectively, the “Underwriters”), to increase the size of its previously announced bought deal private placement to 51,725,000 common shares of the Company (the “Common Shares“) at a price of $0.87 per Common Share (the “Offering Price”) for gross proceeds of $45,000,750 (the “Offering“).

The Company has also granted the Underwriters an option to purchase up to an additional 5,747,200 Common Shares at the Offering Price for additional gross proceeds of up to $5,000,064 exercisable, in whole or in part, at any time up to 48 hours prior to the closing of the Offering (the “Underwriter Option“).

The net proceeds of the Offering will be used to advance the Hercules Project, as well as for working capital and general corporate purposes.

The Common Shares will be offered by way of private placement pursuant to applicable exemptions from prospectus requirements in each of the provinces of Canada, other than Quebec, and in such other jurisdictions as may be mutually agreed between the Company and the Underwriters. It is anticipated that closing of the Offering will occur on or about November 12, 2026 or such other date or dates as the Company and the Underwriters may agree. The Offering is subject to the satisfaction of certain conditions, including receipt of all applicable regulatory approvals including the conditional approval of the TSX Venture Exchange. The securities to be issued under the Offering will be subject to a hold period expiring four months and one day from the applicable closing date in accordance with applicable Canadian securities laws.

About Hercules Metals Corp.

Hercules Metals Corp. (TSXV: BIG) (OTCQB: BADEF) is an exploration Company focused on developing America’s newest porphyry copper district, in Idaho.

The 100% owned Hercules Project, located northwest of Cambridge, hosts the Leviathan porphyry copper system, one of the most important new discoveries in the country to date. The Company is well positioned for growth through continued drilling, supported by a strategic investment from Barrick Mining Corporation.

With the potential for significant scale, the Company’s management and board of directors aims to deliver value to shareholders through proven discovery success.

For further information please contact:

George Ogilvie
President and CEO
Telephone +1 (416) 723-0458
Email: gogilvie@herculesmetals.com

Alison Dwoskin
VP Investor Relations
Telephone: +1 (647) 233-4348
Email: adwoskin@herculesmetals.com

This press release does not constitute an offer to sell or a solicitation of an offer to buy any of the securities in the United States. Any securities referred to herein have not and will not be registered under the United States Securities Act of 1933, as amended (the “U.S. Securities Act“) or any state securities laws and may not be offered or sold within the United States or to U.S. Persons unless registered under the U.S. Securities Act and applicable state securities laws of an exemption from such registration is available.

Cautionary Statements Regarding Forward-Looking Information

All statements, other than statements of historical fact, contained or incorporated by reference in this press release constitute “forward-looking statements” and “forward-looking information” (collectively, “forward-looking statements”) within the meaning of applicable Canadian and United States securities legislation. Generally, forward-looking statements can be identified by the use of forward-looking terminology such as “assumption”, “believe”, “developing”, “estimate”, “expectation”, “exploration”, “focused”, “forward”, “future”, “intended”, “may”, “potential”, “project”, “, and “will”, or variations of such words, and similar such words, expressions or statements that certain actions, events, conditions or results will, may, could, or should (or not) be achieved, occur, provide, result or support in the future, or which, by their nature, refer to future events. In some cases, forward-looking information may be stated in the present tense, such as in respect of current matters that may be continuing, or that may have a future impact or effect. Forward-looking statements in this press release may include statements regarding the Offering, the use of proceeds of the Offering, the ability to obtain necessary approvals in respect of the Offering, including the conditional approval of the TSX Venture Exchange.

Although the Company believes the forward-looking statements contained in this press release are reasonable, there can be no assurance that those forward-looking statements will prove to be correct, and any forward-looking statements by the Company are not guarantees of future actions, results or performance. Forward-looking statements are based on assumptions, estimates, expectations, information and opinions, which are considered reasonable and represent best judgment based on available facts, as of the issuance of this press release. If such assumptions, estimates, expectations and opinions prove to be incorrect, actual and future results may be materially different than expressed or implied in the forward-looking statements. The assumptions, estimates, expectations and opinions contained in this press release which may prove to be incorrect include those set forth in this press release, as well as those stated in the Company’s other public disclosure, including its Management’s Discussion and Analysis (together with the accompanying financial statements) for the year ended December 31, 2025 and for the most recently completed financial quarter (collectively, the “Public Disclosure”), available on the Company’s website at www.herculesmetals.com and under its issuer profile at www.sedarplus.ca. Forward-looking statements, by their nature, are inherently subject to known and unknown risks, uncertainties, contingencies and other factors which may cause the Company’s actual results, activity, performance, developments or achievements, or other future events, to be materially different from any future results, activity, performance, developments or achievements expressed or implied by such forward-looking statements. Examples of such assumptions, estimates, expectations, opinions, risks, uncertainties, contingencies and other factors include those identified herein as well as those set forth in the Public Disclosure, available on the Company’s website at www.herculesmetals.com and/or under its issuer profile at www.sedarplus.ca. Although the Company has attempted to identify important factors that could cause actual actions, events or results to differ materially from those contained in forward-looking statements, there may be other factors that cause actions, events or results to differ from those anticipated, estimated or intended. Forward-looking statements contained herein are made as of the issuance of this press release (or as otherwise expressly specified) and the Company disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or results or otherwise, except as required by applicable securities laws. There can be no assurance that such information will prove to be accurate, as actual results and future events could differ materially from forward-looking statements. Accordingly, readers should not place undue reliance on forward-looking statements. The forward-looking statements referenced or contained in this press release are expressly qualified by these Cautionary Statements as well as the cautionary statements and/or notes in the Public Disclosure.

Neither the TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this press release.

TORONTO, Oct. 23, 2026 (GLOBE NEWSWIRE) — Middlefield Global Dividend Growers ETF (TSX: MDIV) (the “Fund”) is pleased to announce that distributions for the fourth quarter of 2026 will be payable to unitholders of Middlefield Global Dividend Growers ETF as follows:

Record Date	Payable Date	Distribution Per Trust Unit
October 31, 2026	November 13, 2026	$0.06
November 30, 2026	December 15, 2026	$0.06
December 31, 2026	January 15, 2027	$0.06

The trust units trade on the Toronto Stock Exchange under the symbol MDIV.

The Fund offers a distribution reinvestment plan (“DRIP”) for unitholders which provides unitholders with the ability to automatically reinvest distributions, commission free, and realize the benefits of compound growth. Unitholders can enroll in the DRIP program by contacting their investment advisor.

About Middlefield

Founded in 1979, Middlefield is an independent, income-focused asset manager with offices in Toronto, Canada and London, England. For more than four decades, we have helped investors generate income and build wealth through active management and disciplined risk management. Today, Middlefield offers a growing range of investment strategies across global fixed income and equities, delivered through Canadian and European exchange-traded funds, mutual funds and alternative investment solutions for individual and institutional investors. Supported by an experienced investment team and a culture of independent thinking, Middlefield seeks to deliver attractive risk-adjusted returns, sustainable income and long-term capital appreciation across market cycles.

For further information, please visit our website at www.middlefield.com or contact our Sales and Marketing Department at 1.888.890.1868.

This press release contains forward-looking information. The forward-looking information contained in this press release is based on historical information concerning distributions and dividends paid on the securities of issuers historically included in the portfolio of the Fund. Actual future results, including the amount of distributions paid by the Fund, may differ from the monthly distribution amount. Specifically, the income from which distributions are paid may vary significantly due to: changes in portfolio composition; changes in distributions and dividends paid by issuers of securities included in the Fund’s portfolio from time to time; there being no assurance that those issuers will pay distributions or dividends on their securities; the declaration of distributions and dividends by issuers of securities included in the portfolio will generally depend upon various factors, including the financial condition of each issuer and general economic and stock market conditions; the level of borrowing by the Fund; and the uncertainty of realizing capital gains.  The risks, uncertainties and other factors that could influence actual results are described under “Risk Factors” in the Fund’s prospectus and other documents filed by the Fund with the Canadian securities regulatory authorities. The forward-looking information contained in this press release constitutes the Fund’s current estimate, as of the date of this press release, with respect to the matters covered hereby. Investors and others should not assume that any forward-looking statement contained in this press release represents the Fund’s estimate as of any date other than the date of this press release.

62.5% Confirmed Objective Response Rate (ORR) and 29.2% Complete Response (CR) Rate in Final Phase 2 Analysis

Median Overall Survival (OS) Not Reached at More than 4 Years of Median Follow-up

Oral Presentation at the European Society for Medical Oncology (ESMO) Congress 2026 Reinforces Ongoing TILVANCE-301 Phase 3 Trial

PHILADELPHIA and MADRID, Oct. 23, 2026 (GLOBE NEWSWIRE) — Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a commercial biotechnology company focused on innovating, developing, and delivering novel polyclonal tumor infiltrating lymphocyte (TIL) therapies for patients with cancer, today announced that one-time lifileucel combined with pembrolizumab demonstrated a 62.5% ORR and a 29.2% CR rate, with median OS not reached at 50.9 months of median study follow-up in the final Phase 2 analysis in frontline advanced melanoma. The Phase 2 results were presented on October 23, 2026 in a Proffered Paper oral session at the ESMO Congress 2026 in Madrid, Spain.

In frontline advanced melanoma, approximately half of patients treated with combination immune checkpoint inhibitor (ICI) therapy do not achieve long-term benefit, a widely recognized unmet need.¹ Following successful adoption of lifileucel in the post-anti-PD-1 therapy setting, this Phase 2 data supports the earlier use and potential approval of lifileucel plus pembrolizumab in frontline advanced melanoma. Iovance estimates that 70,000 patients with frontline advanced melanoma are addressable each year in global markets with high prevalence.²

ESMO Presentation Highlights: Cohort 1A of the IOV-COM-202 Trial (NCT03645928)

IOV-COM-202 is a multicohort, multicenter Phase 2 trial of lifileucel plus pembrolizumab in patients with solid tumors. The final analysis in frontline advanced melanoma (Cohort 1A) included 24 patients treated with one-time lifileucel that met pre-determined manufacturing specifications and pembrolizumab monotherapy for up to 24 months.

The physician-assessed confirmed ORR by RECIST v1.1 was 62.5% (15/24; 95% CI: 40.6, 81.2), including a 29.2% CR rate. The disease control rate was 83.3% (20/24; 95% CI: 62.6, 95.3). Median duration of response (DOR) was not reached (range: 4.3 to 57.7+ months) at a median follow-up of 26.9 months for DOR.

Median progression-free survival (PFS) was 19.8 months (95% CI: 3.6 months to not reached). Median PFS after second line of therapy was 34.3 months (95% CI: 6.8 months to not reached), indicating that subsequent systemic therapy remains feasible after frontline lifileucel and pembrolizumab, including additional ICI therapy. Median OS was not reached (95% CI: 19.2 months to not reached) at a median study follow-up of 50.9 months.

Safety was consistent with the underlying disease and known safety profiles of one-time lifileucel and pembrolizumab. Late adverse events were consistent with continuous use of pembrolizumab monotherapy, further differentiating lifileucel plus pembrolizumab from ICI combinations used in the frontline setting.

“About half of patients do not experience lasting benefit with frontline combination immunotherapy for advanced melanoma,” stated Dr. Andrew J.S. Furness, Consultant Medical Oncologist and Solid Tumour Cellular Therapy Lead at The Royal Marsden National Health Service Foundation Trust, Leader of the Cellular Therapy and Translational Immunology Group at The Institute of Cancer Research, London, and Principal Investigator in IOV-COM-202 and TILVANCE-301 trials. “A single administration of lifileucel plus pembrolizumab demonstrated compelling response rates and durability that compare favorably to other ICI combination approaches in frontline advanced melanoma, with median overall survival not reached at more than four years of follow-up. These remarkable Phase 2 results provide a strong scientific rationale to investigate earlier treatment with lifileucel in the TILVANCE-301 trial.”

Translational analyses support the positive clinical results in Cohort 1A. T-cell receptor (TCR) sequencing detected clones from the infused lifileucel product in the peripheral blood for as long as 12 months after infusion (n=13), consistent with the strong DOR benefit of lifileucel.

Noah Berkowitz, M.D., Ph.D., Chief Medical Officer of Iovance, stated, “The final Cohort 1A results demonstrate unprecedented efficacy and a potentially best-in-class clinical profile for lifileucel combined with pembrolizumab in frontline advanced melanoma. These data, together with supportive translational findings, reinforce the importance of our ongoing TILVANCE-301 Phase 3 randomized trial to support a new approval for lifileucel in frontline advanced melanoma.”

The presentation is available at www.iovance.com. Iovance will also present the first clinical data for lifileucel in soft tissue sarcomas in a Rapid Oral presentation on Monday, October 26, 2026 (Abstract #3725RO).

About TILVANCE

TILVANCE-301 (NCT05727904) is a Phase 3, multicenter, open-label, randomized, parallel group, treatment study to assess the efficacy and safety of lifileucel in combination with pembrolizumab compared with pembrolizumab alone in participants with untreated, unresectable or metastatic melanoma. The trial is enrolling at more than 80 sites in the U.S., Canada, Europe, and Asia-Pacific. The dual primary endpoints are ORR and PFS assessed by independent review committee. TILVANCE-301 is designed to support approval for lifileucel in combination with pembrolizumab in frontline advanced melanoma and to serve as the confirmatory trial for full U.S. approval of Amtagvi® in previously treated advanced melanoma.

About Iovance Biotherapeutics, Inc.

Iovance Biotherapeutics, Inc. is the global leader in innovating, developing, and delivering tumor infiltrating lymphocyte (TIL) cell therapies for patients with solid tumors. Amtagvi® (lifileucel) is the first FDA-approved, one-time treatment for previously treated advanced melanoma, now approved in three global markets and available at nearly 100 authorized treatment centers (ATCs). The Iovance TIL platform spans registrational trials and next-generation programs in additional solid tumors, including gene-edited and IL-12 tethered TIL therapies, next-generation IL-2, and precision immuno-oncology approaches. As the first and only company to take TIL therapy from concept to a broadly accessible commercial treatment, Iovance operates as an end-to-end cell therapy company, anchored by fully owned, centralized U.S.-based manufacturing that is scaled to serve thousands of cancer patients worldwide each year. Headquartered in Pennsylvania with offices and laboratories in California and Florida, Iovance serves patients at ATCs and clinical sites across almost the entire U.S. and in many countries around the world. For more information, please visit www.iovance.com.

Amtagvi® and its accompanying design marks, Proleukin®, Iovance®, and IovanceCares™ are trademarks and registered trademarks of Iovance Biotherapeutics, Inc. or its subsidiaries. All other trademarks and registered trademarks are the property of their respective owners.

Information on Iovance’s broad, industry-leading patent portfolio is available on the Intellectual Property page on www.iovance.com.

About the ESMO Congress

The ESMO Congress is organized by the European Society for Medical Oncology (ESMO) and is one of the world’s most influential annual oncology meetings, bringing together more than 37,000 clinicians, researchers, patient advocates, and industry representatives from around the world. The ESMO Congress 2026 takes place October 23–27, 2026, at IFEMA Madrid, Spain, and features presentations of practice-changing clinical data, translational science, and educational programming across all major tumor types. For more information, visit www.esmo.org.

References

1. Larkin J, et al. N Engl J Med. 2019;381:1535-46.
2. SEER and GLOBOCAN epidemiology data and internal data on file.

Forward-Looking Statements

Certain matters discussed in this press release are “forward-looking statements” of Iovance Biotherapeutics, Inc. (hereinafter referred to as the “Company,” “we,” “us,” or “our”) within the meaning of the Private Securities Litigation Reform Act of 1995 (the “PSLRA”). Without limiting the foregoing, we may, in some cases, use terms such as “predicts,” “believes,” “potential,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “forecast,” “guidance,” “outlook,” “may,” “can,” “could,” “might,” “will,” “should,” or other words that convey uncertainty of future events or outcomes and are intended to identify forward-looking statements. Forward-looking statements are based on assumptions and assessments made in light of management’s experience and perception of historical trends, current conditions, expected future developments, and other factors believed to be appropriate. Forward-looking statements in this press release are made as of the date of this press release, and we undertake no duty to update or revise any such statements, whether as a result of new information, future events, or otherwise. Forward-looking statements are not guarantees of future performance and are subject to risks, uncertainties, and other factors, many of which are outside of our control, that may cause actual results, levels of activity, performance, achievements, and developments to be materially different from those expressed in or implied by these forward-looking statements. Important factors that could cause actual results, developments, and business decisions to differ materially from forward-looking statements are described in the sections titled “Risk Factors” in our filings with the U.S. Securities and Exchange Commission, including our most recent Annual Report on Form 10-K and Quarterly Reports on Form 10-Q, and include, but are not limited to, the following substantial known and unknown risks and uncertainties inherent in our business: the risks related to our ability to successfully commercialize our products; the size of the addressable patient populations for, and the acceptance by the market of, our products and product candidates, if approved, and their potential pricing and/or reimbursement by payors, and whether such acceptance is sufficient to support continued commercialization or development of our products or product candidates; the risk regarding our ability to manufacture our therapies at our iCTC facility, including the risk that our ability to increase manufacturing capacity at our facility may adversely affect our commercial supply or clinical supply; the risks related to our ability to obtain, maintain and enforce patent and other intellectual property protection for our products and product candidates; the risk that the successful development or commercialization of our products may not generate sufficient revenue from product sales, and we may not become profitable in the near term, or at all; the risks related to the timing of and our ability to successfully develop, submit, obtain, or maintain regulatory authority approval of our product candidates; whether clinical trial results from our clinical studies and cohorts, and meetings with regulatory authorities, may support registrational studies and subsequent approvals by regulatory authorities, including the risk that our registrational trials, including TILVANCE-301, may be delayed, may not meet their primary endpoints, or may not support approval; clinical results, whether preliminary, interim, or final, which may include efficacy and safety results, from clinical trials or cohorts may not be reflected in the final analyses of our ongoing clinical trials or subgroups within these trials or in other prior or future trials or cohorts, including the risk that the Cohort 1A results of IOV-COM-202 may not be predictive of results in the ongoing TILVANCE-301 trial; the risk that we may be required to conduct additional clinical trials or modify ongoing or future clinical trials based on feedback from regulatory authorities; the risk that our interpretation of the results of our clinical trials or communications with regulatory authorities may differ from the interpretation of such results or communications by such regulatory authorities or others; the risk that clinical data from ongoing clinical trials of Amtagvi will not continue or be repeated in ongoing or planned clinical trials or may not support regulatory approval or renewal of authorization; the risk that unanticipated expenses may decrease our estimated cash balances and forecasts and increase our estimated capital requirements; the risk that we may not be able to recognize revenue for our products; the risk that Proleukin revenues, and other factors such as the number of ATCs, may not serve as a leading indicator for Amtagvi revenues; the risks regarding our anticipated operating and financial performance, including our financial guidance and projections; the effects of global and domestic geopolitical factors or public health events; and other factors, including general economic conditions and regulatory developments, not within our control.

CONTACTS

Investors
IR@iovance.com
650-260-7120 ext. 150

Media
PR@iovance.com
650-260-7120 ext. 150

• Median overall survival of 15.9 months in Cyclin E1-positive PROC, with 1–5 prior lines of therapy; safety profile in DENALI Part 1b was consistent with prior reporting
• Median relative dose intensity was 84.6%, confirming high overall exposure to azenosertib
• DENALI Part 1b interim analysis adds to the body of evidence supporting Cyclin E1 protein expression as a predictive biomarker for azenosertib in platinum-resistant ovarian cancer

SAN DIEGO, Oct. 23, 2026 (GLOBE NEWSWIRE) — Zentalis^® Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical oncology innovator advancing late-stage development of investigational first-in-class WEE1 inhibitor azenosertib as a biomarker-driven treatment approach for ovarian cancer, today presented results from an interim analysis of the DENALI Part 1b study (GOG-3066) as of a May 22, 2026 data cutoff, including the first overall survival analysis for azenosertib, at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid, Spain.

“These data continue to build the body of evidence supporting azenosertib as a potential treatment in Cyclin E1-positive platinum-resistant ovarian cancer, underpinning our development approach through the ongoing registration-intended DENALI Part 2 and ASPENOVA Phase 3 confirmatory trials. For patients with Cyclin E1-positive PROC who have limited effective treatment options, we are working to deliver something that has not existed — a targeted, oral treatment that offers more convenience and choice,” said Julie Eastland, Chief Executive Officer of Zentalis Pharmaceuticals.

“The overall survival results from DENALI Part 1b are particularly meaningful given the poor prognosis associated with Cyclin E1-positive tumors and the heavily pretreated nature of this trial patient population,” said Fiona Simpkins, M.D., Professor at the University of Pennsylvania Perelman School of Medicine and Lead Investigator for the DENALI study and The GOG Foundation, Inc. (GOG-F). “The separation in median overall survival between Cyclin E1-positive and Cyclin E1-negative patients — 15.9 months versus 7.5 months — strongly supports Cyclin E1 protein expression as a clinically relevant and predictive patient selection biomarker for azenosertib. Taken together with the response data and manageable adverse events, these findings provide important evidence supporting continued development of azenosertib in this biomarker-selected population with high unmet need.”

Updated DENALI Part 1b Efficacy Results
As of the May 22, 2026 data cutoff, DENALI Part 1b enrolled 102 patients with PROC regardless of Cyclin E1 protein expression who had received between one and five prior lines of therapy, with prior bevacizumab required. This was a heavily pretreated population: 97% had received a taxane, 91% bevacizumab, 55% a PARP inhibitor, and 15% mirvetuximab soravtansine, with a median of three prior lines of therapy. Cyclin E1 status was retrospectively determined by immunohistochemistry using a proprietary cutoff, with 94 patients evaluable (Cyclin E1 IHC-positive: n=48, 51%; Cyclin E1 IHC-negative: n=46).

Overall Survival (OS):

• Cyclin E1 IHC-positive (n=48): median OS of 15.9 months (95% CI, 8.7–21.2); 31 events had occurred (65%)
• Cyclin E1 IHC-negative (n=46): median OS of 7.5 months (95% CI, 5.8–12.3); 34 events had occurred (74%)

Objective Response Rate (ORR) and Duration of Response (DOR):

• ORR in response-evaluable Cyclin E1 IHC-positive patients (n=43): 37.2% (95% CI, 23.0–53.3)
• ORR in all Cyclin E1 IHC-positive patients (n=48): 33.3% (95% CI, 20.4–48.4)
• Median DOR: 5.5 months (95% CI, 4.5–15.9)

The updated ORR includes a patient with a confirmed response after the prior cutoff. The current median DOR of 5.5 months reflects a more mature dataset with less censoring than the prior cutoff, including two patients with particularly durable responses exceeding 15 and 20 months.

Safety
The safety profile was consistent with prior reporting. The most common treatment-related adverse events (TRAEs) were nausea, fatigue, diarrhea, thrombocytopenia, decreased appetite, anemia, and neutropenia. The most common non-hematologic Grade ≥3 TRAE was fatigue (16%). Grade ≥3 hematologic TRAEs included thrombocytopenia (12%), anemia (11%), and neutropenia (11%).

The median relative dose intensity was 84.6%, confirming that overall exposure to azenosertib remained high despite dose modifications. TRAEs led to dose interruption in 56.9% of patients, dose reduction in 43.1%, and discontinuation in 19.6%. Serious TRAEs occurred in 21.6% of patients.

The ESMO slides inclusive of the full interim analysis dataset presented at the medical meeting are available on the Zentalis website under scientific publications at the following link: https://zentalis.com/science/scientific-publications/

About the DENALI Clinical Trial
DENALI is a multi-part Phase 2 registration-intended clinical trial (NCT05128825, GOG-3066) studying azenosertib in patients with PROC, conducted in collaboration with The GOG Foundation, Inc. (GOG-F).

Part 1b enrolled 102 patients with PROC regardless of Cyclin E1 protein expression, all treated at 400 mg QD 5:2 (five days of once-daily administration of azenosertib, followed by two days without azenosertib). The primary endpoint was objective response rate per RECIST v1.1; secondary endpoints included duration of response, progression-free survival, overall survival, and safety.

Part 2 is prospectively enrolling PROC patients with Cyclin E1 protein overexpression based on Zentalis’ proprietary immunohistochemistry cutoff. Part 2, in total, is designed to support accelerated approval, pending positive study outcomes and further discussions with the FDA. The study design consists of the following parts:

• Part 2a: Dose confirmation evaluated two doses, 300 mg QD 5:2 and 400 mg QD 5:2, with approximately 30 patients enrolled per dose group. 400 mg QD 5:2 was selected as the optimal monotherapy dose. Recruitment at the 300 mg QD 5:2 dose level has been discontinued. All patients enrolled in Part 2a will contribute to the overall safety database submitted to the FDA.
• Part 2b: Enrollment expansion at the selected 400 mg QD 5:2 dose up to approximately 100 patients, including patients at this dose in Part 2a. Enrollment in this cohort is complete.
• Part 2c: Expansion of the study population, expected to enroll approximately 40 patients previously treated with a taxane-containing regimen for PROC. This cohort is currently enrolling.

For physician and patient information about the DENALI trial, please visit www.denalitrial.com.

About ASPENOVA Clinical Trial
ASPENOVA is a Phase 3 randomized, confirmatory clinical trial designed to support full approval of azenosertib in patients with Cyclin E1-positive PROC. The trial is expected to enroll approximately 420 patients and compare azenosertib monotherapy at 400mg QD 5:2 to investigator’s choice of standard-of-care single-agent chemotherapy (paclitaxel, pegylated liposomal doxorubicin [PLD], gemcitabine, or topotecan) in this biomarker-selected population. The primary endpoint is progression-free survival (PFS); key secondary endpoints include overall survival (OS) and overall response rate (ORR). The trial design was based on feedback from the U.S. FDA regarding requirements for seeking approval under the accelerated approval pathway and requirements to support potential conversion to full approval.

About Azenosertib
Azenosertib is an investigational, potentially first-in-class, selective, and orally bioavailable inhibitor of WEE1 currently being evaluated in clinical studies in ovarian cancer and additional tumor types. WEE1 acts as a master regulator of the G1-S and G2-M cell cycle checkpoints, through negative regulation of both CDK1 and CDK2, to prevent replication of cells with damaged DNA. By inhibiting WEE1, azenosertib enables cell cycle progression, despite high levels of DNA damage, thereby resulting in the accumulation of DNA damage and leading to mitotic catastrophe and cancer cell death.

Azenosertib is in late-stage development as a potential treatment for Cyclin E1-positive platinum-resistant ovarian cancer (PROC). There is currently no approved treatment option specifically for this biomarker-selected population which comprises approximately 50% of PROC patients. Cyclin E1 protein overexpression has been established as a sensitive and specific predictive biomarker for identifying patients who could potentially derive benefit from azenosertib treatment.

About Zentalis Pharmaceuticals
Zentalis is a clinical oncology innovator developing a treatment approach for ovarian cancer and multiple tumor types. Leveraging therapeutics development and biomarker expertise, Zentalis is advancing monotherapy and combination studies of its investigational first-in-class WEE1 inhibitor, azenosertib. Focused on translating WEE1 science into clinical practice, we aim to equip physicians with a targeted, non-chemo, orally available medicine that enhances treatment experience, choice, and outcomes. Our mission: to unburden cancer patients with more convenience and care.​

For more information, please visit www.zentalis.com. Follow Zentalis on LinkedIn at www.linkedin.com/company/zentalis-pharmaceuticals

Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, as amended. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including, but not limited to, statements regarding the continued development of azenosertib; the clinical and therapeutic potential of azenosertib; the potential for azenosertib to be first-in-class; the broad franchise potential of azenosertib; the Company’s biomarker-driven strategy for azenosertib, including the ability of Cyclin E1 to be a highly selective and predictive biomarker for response to azenosertib; and our participation in conference presentations. The terms “anticipate,” “advance,” “believe,” “design,” “develop,” “expect,” “intent,” “look forward,” “on track,” “plan,” “position,” “potential,” “runway,” “strategy,” “support,” “target,” “upcoming,” and “will” and similar references are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: our limited operating history, which may make it difficult to evaluate our current business and predict our future success and viability; we have and expect to continue to incur significant losses; our need for additional funding, which may not be available; our substantial dependence on the success of azenosertib; our plans, including the costs thereof, of development of companion diagnostics; the outcome of preclinical testing and early trials may not be predictive of the success of later clinical trials; potential unforeseen events during clinical trials could cause delays or other adverse consequences; risks relating to the regulatory approval process or ongoing regulatory obligations; our product candidates may cause serious adverse side effects; inability to maintain our collaborations, or the failure of these collaborations; our reliance on third parties; effects of significant competition; the possibility of system failures or security breaches; risks relating to intellectual property; our ability to attract, retain and motivate qualified personnel, and risks relating to management transitions; significant costs as a result of operating as a public company; and the other important factors discussed under the caption “Risk Factors” in our most recently filed periodic report on Form 10-K or 10-Q and subsequent filings with the U.S. Securities and Exchange Commission (SEC) and our other filings with the SEC. Any such forward-looking statements represent management’s estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change.

ZENTALIS^® and its associated logo are trademarks of Zentalis and/or its affiliates. All website addresses and other links in this press release are for information only and are not intended to be an active link or to incorporate any website or other information into this press release. 

Contact: 
Aron Feingold
VP, Investor Relations & Corporate Communications
ir@zentalis.com