On April 17, 2026 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, reported data from two posters being presented at the 2026 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place April 17-22, 2026, in San Diego, CA. The data show encouraging preclinical activity of azenosertib in triple-negative breast cancer (TNBC) and highlight the poor prognosis of Cyclin E1-positive ovarian cancer patients with currently available treatments in a real-world data analysis.

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Compelling Preclinical Activity in Triple-Negative Breast Cancer with Azenosertib

"The preclinical data in triple-negative breast cancer being presented at AACR (Free AACR Whitepaper) showed that azenosertib combinations can induce complete tumor responses in a model resistant to emerging ADC therapies, supporting the potential to broaden the impact of azenosertib beyond ovarian cancer," said Julie Eastland, Chief Executive Officer of Zentalis. "This includes potential development of azenosertib through differentiated combination strategies with antibody-drug conjugates (ADCs) and chemotherapy. As ADCs advance toward first-line use in TNBC, effective post-ADC treatment strategies represent a growing unmet need that azenosertib combinations may be uniquely positioned to fill. Our data suggest azenosertib may achieve this through multiple mechanisms – possibly resensitizing tumors to chemotherapy, enhancing the responses to ADC, and extending the duration of response – which is an exciting potential future direction for our pipeline."

Preclinical evidence supports azenosertib as a therapeutic strategy in TNBC:
•TNBC cell lines showed higher Cyclin E1 expression and greater sensitivity to WEE1 inhibition compared to other breast cancer cell lines
oAzenosertib monotherapy demonstrated meaningful antitumor activity across a diverse panel of 12 TNBC in vivo xenograft models (42-99% tumor growth inhibition)
•In a patient-derived xenograft model of TNBC with clinical resistance to sacituzumab govitecan, an approved topoisomerase 1 inhibitor (TOPO1i) ADC, azenosertib + enfortumab vedotin (EV):
oInduced complete responses in 7 of 8 mice (87.5%); 5 mice did not progress after treatment discontinuation
oPrevented tumor progression in 8 of 8 mice for more than 52 days compared to 100% progression observed within 30 days with EV alone
oDrove deep tumor regression in mice models refractory to sacituzumab govitecan or trastuzumab deruxtecan with large tumor volumes (average ~900mm3)

•Combinations of azenosertib with TOPO1i-payload ADCs (sacituzumab govitecan, datopotamab deruxtecan, or trastuzumab deruxtecan) enhanced both depth and duration of response compared to ADC monotherapy in ADC-naïve models
•Azenosertib + paclitaxel restored substantial sensitivity to paclitaxel in a model resistant to both paclitaxel and TOPO1i ADCs (51% tumor growth inhibition vs. 16% with paclitaxel alone)

Cyclin E1 Protein Overexpression Characterizes Ovarian Cancer Patients with Poor Prognosis

"The real-world data being presented at AACR (Free AACR Whitepaper) provide important validation that Cyclin E1-positive ovarian cancer patients face a particularly challenging disease trajectory with standard-of-care therapies," said Ingmar Bruns, M.D., Chief Medical Officer of Zentalis. "The consistency of worse outcomes across independent cohorts and multiple treatment settings underscores the significant unmet need in this population. These findings provide important context for Zentalis’ registration-intended DENALI and ASPENOVA studies, which are evaluating WEE1 inhibition with azenosertib monotherapy as a targeted approach for the Cyclin E1-positive population that currently has limited effective treatment options."

Real-world data from two independent cohorts (Tempus Lens Ovarian cancer dataset and Zentalis’ historical clinical trials) consistently demonstrated that Cyclin E1-positive ovarian cancer patients experience worse clinical outcomes:
•After first-line treatment, Cyclin E1-positive patients, with or without CCNE1 gene amplification, had shorter time to next treatment compared to Cyclin E1-negative patients (13.2 months and 14.9 months, respectively, compared to 19.5 months, p=0.002)
•Cyclin E1-positivity is associated with a trend toward reduced clinical benefit from standard-of-care PROC treatments

AACR Poster Details

Title: "WEE1 Inhibition as a Therapeutic Strategy in Triple-Negative Breast Cancer: Evaluating Single Agent and Combination Activity of Azenosertib in Preclinical Models"
Abstract Number: 2012
Date/Time: Monday, April 20, 2026, 2:00 p.m. – 5:00 p.m. PDT
Presenting Author: Alexandra Levy, MS

Title: "Real-World Treatment Patterns and Outcomes Reveal Distinct Clinical Trajectories of Patients with Cyclin E1-Positive Ovarian Cancer"
Abstract Number: 1708
Date/Time: Sunday, April 19, 2026, 2:00 p.m. – 5:00 p.m. PDT
Presenting Author: Jinkil Jeong, PhD

The posters can be accessed on the Supporting Publications page of the Zentalis website.

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, based on retrospective analysis of azenosertib studies in PROC. Validation of the Cyclin E1 companion diagnostic assay is ongoing in the DENALI and ASPENOVA trials.

Azenosertib has been granted Fast Track Designation by the U.S. FDA for the treatment of patients with Cyclin E1-positive platinum-resistant ovarian cancer. Fast Track Designation is intended to facilitate the development and expedite the review of therapies that have the potential to treat serious conditions and address unmet medical needs.

(Press release, Zentalis Pharmaceuticals, APR 17, 2026, View Source [SID1234664477])

On April 17, 2026 Volastra Therapeutics, a clinical-stage oncology company pioneering therapies targeting chromosomal instability (CIN), reported multiple scientific disclosures coinciding with the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2026, taking place April 17–22 in San Diego, California. The data define an Rb pathway–driven pan-cancer development framework for KIF18A inhibitors and highlight a proprietary p16 IHC biomarker approach designed to translate that strategy clinically, reinforcing Volastra’s leadership in advancing CIN biology into therapeutic opportunity.

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Separate from its AACR (Free AACR Whitepaper) 2026 presentation, Volastra has posted "KIF18A Inhibition as a Therapeutic Strategy in Cancers with Rb Pathway Inactivation" (Andreu et al. DOI: View Source – preprint publication). Drawing on what is believed to be one of the largest datasets of its kind, the work identifies Rb pathway inactivation as the mechanistic basis of response to KIF18A inhibition and establishes a development path that extends well beyond high-grade serous ovarian cancer.

The study includes clinical data from a substantial cohort of 79 heavily pretreated patients with high-grade serous ovarian cancer treated with either of two distinct KIF18A inhibitors, sovilnesib and VLS-1488. The concordance of the biomarker-defined signal across both agents is particularly compelling and argues against a drug-specific observation. Biomarker-positive tumors were distinguished by marked enrichment for objective responses, durable disease control, and longer progression-free survival, yielding a sharp clinical separation from biomarker-negative disease and strongly supporting both the biomarker strategy and prospective clinical development.

These findings reposition KIF18A inhibition from a histology-defined opportunity into a pan-cancer synthetic lethal strategy centered on one of the most commonly disrupted tumor suppressor pathways in human cancer. This creates a credible path across what is estimated to represent approximately 15% of human cancers. Within that biology, Volastra has identified a proprietary p16 IHC biomarker strategy that enriches for response to its KIF18A inhibitors and provides a practical route to clinical translation.

"The data provide a strong scientific rationale for using p16 status to identify patients most likely to benefit from KIF18A inhibition," said David Southwell, Chief Executive Officer of Volastra Therapeutics. "Importantly, this work reframes KIF18A inhibition from a narrow single cancer-type opportunity into a broader pan-cancer strategy grounded in Rb pathway biology. This p16 biomarker approach provides a practical way to translate that insight into clinical development and patient selection."

AACR Poster Highlights Clear Synergy with Taxanes and Other Microtubule-Targeting Agents

Volastra will also present an official AACR (Free AACR Whitepaper) poster titled "Combination of VLS-1488 and taxanes induces anti-tumor synergistic effect in cancer cells" in the Experimental and Molecular Therapeutics, Novel Antitumor Agents 1 Session on April 19 from 2-5PM Pacific Time (PT) (Poster section 17, poster 18). The presentation will highlight preclinical combination data showing clear synergistic activity between KIF18A inhibition and taxanes and other microtubule-targeting agents. These findings support a development strategy that could extend KIF18A inhibitors into earlier lines of therapy, including combination approaches in frontline settings.

"The totality of these data help define both the monotherapy and combination development paths for KIF18A inhibitors," said Samuel F. Bakhoum, M.D., Ph.D., Co-Founder and Chief Scientific Officer of Volastra Therapeutics. "With this new mechanistic understanding of KIF18A inhibitor sensitivity, it is evident that the biomarker data will help us identify patients most likely to benefit from monotherapy, while the combination findings point to a precision-based approach to identify the most rational therapeutic partners for development in earlier line settings."

Separately, Dr. Bakhoum, also an adjunct faculty member at the Geisel School of Medicine at Dartmouth, will chair an AACR (Free AACR Whitepaper) educational session "Chromosomal Instability in Cancer: From Mechanism to Therapy and Clinical Translation" on Saturday, April 18, 2026, in his academic capacity. The session reflects the field’s growing appreciation of CIN as both a driver of aggressive disease and a source of therapeutic vulnerability.

"This momentum underscores the growing recognition of CIN biology and the increasing importance of CIN-directed therapeutic strategies across oncology," Dr. Bakhoum said.

(Press release, Volastra Therapeutics, APR 17, 2026, View Source [SID1234664476])

On April 17, 2026 Soley Therapeutics, a biotechnology company advancing novel therapeutics informed by integrated cell stress biology, reported the presentation of new preclinical data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2026 highlighting the anti-tumor activity of STX-6398, a first-in-class, oral small-molecule modulator of cytoskeleton-associated protein 2 (CKAP2) pathway. CKAP2 is an intrinsically disordered protein that has been historically considered undruggable and is central to malignant progression.

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"STX-6398 is one of several potential first-in-class candidates rapidly found using our discovery platform," said Yerem Yeghiazarians, M.D., Co-Founder and Chief Executive Officer of Soley. "CKAP2 is implicated in multiple aspects of malignant progression, and its role across tumor types makes it an attractive target for therapeutic intervention. The preclinical profile of STX-6398, including biomarker-linked activity, oral dosing, and in vivo tolerability, supports continued evaluation as a potential therapeutic approach in CKAP2-expressing cancers."

Preclinical studies of STX-6398 demonstrate selective anti-tumor activity. In a 300-tumor cell line panel, sensitivity to STX-6398 correlated with CKAP2 protein abundance across cancer types, supporting a biomarker-linked therapeutic approach in both hematologic and solid tumors. Mechanistic studies showed that STX-6398 modulates CKAP2-associated pathways, including focal adhesion kinase (FAK) signaling, resulting in reduced cell migration, disruption of microtubule dynamics, and induction of cell cycle arrest. Additional studies demonstrated inhibition of angiogenesis and maintenance of activity under hypoxic conditions.

In vivo, oral administration of STX-6398 demonstrated significant anti-tumor activity across multiple xenograft models, including lung and colon cancer, with dose-dependent tumor growth inhibition and regression. The compound was well tolerated in efficacy studies and demonstrated a favorable profile in preclinical safety assessments.

The poster presented at AACR (Free AACR Whitepaper) 2026 titled "CKAP2 Modulation With A Novel Small Molecule Results In Excellent In Vitro And In Vivo Anti-Tumor Activity" is available in the Publications section of the Company’s website at View Source

The poster titled "CKAP2 Modulation With a Novel Small Molecule Results in Excellent In Vitro and In Vivo Anti-Tumor Activity" will be presented at AACR (Free AACR Whitepaper) 2026 on April 20 from 2:00 PM to 5:00 PM PDT in Poster Section 15, Poster Number 3043.

(Press release, Soley Therapeutics, APR 17, 2026, View Source [SID1234664475])

On April 17, 2026 Revolution Medicines, Inc. (Nasdaq: RVMD), a late-stage clinical oncology company developing targeted therapies for patients with RAS-addicted cancers, reported the closing of its concurrent upsized public offerings of 12,147,887 shares of its common stock at a public offering price of $142.00 per share and $500.0 million aggregate principal amount of 0.50% convertible senior notes due 2033 (the "notes"). The shares of common stock issued and sold in the common stock offering include 1,584,506 shares issued upon exercise in full by the underwriters of their option to purchase additional shares of common stock at the public offering price, less underwriting discounts and commissions. The gross proceeds from the offerings, before deducting underwriting discounts and commissions and other offering expenses payable by Revolution Medicines, were approximately $2,225.0 million.

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J.P. Morgan, TD Cowen and Guggenheim Securities acted as book-running managers for the note offering and the common stock offering. LifeSci Capital acted as lead manager for the note offering and the common stock offering.

The notes are senior, unsecured obligations of Revolution Medicines and will accrue interest at a rate of 0.50% per annum, payable semi-annually in arrears on May 1 and November 1 of each year, beginning on November 1, 2026. The notes will mature on May 1, 2033, unless earlier repurchased, redeemed or converted. Before February 1, 2033, noteholders will have the right to convert their notes only upon the occurrence of certain events. From, and including, February 1, 2033, noteholders may convert their notes at any time at their election until the close of business on the second scheduled trading day immediately before the maturity date. Revolution Medicines will settle conversions by paying or delivering, as applicable, cash, shares of its common stock or a combination of cash and shares of its common stock, at Revolution Medicines’ election. The initial conversion rate is 5.0302 shares of common stock per $1,000 principal amount of notes, which represents an initial conversion price of approximately $198.80 per share of common stock. The initial conversion price represents a premium of approximately 40.0% over the public offering price per share of common stock in the common stock offering. The conversion rate and conversion price will be subject to adjustment upon the occurrence of certain events.

The notes will be redeemable, in whole or in part (subject to certain limitations), for cash at Revolution Medicines’ option at any time, and from time to time, on or after May 6, 2030 and on or before the 31st scheduled trading day immediately before the maturity date, but only if the last reported sale price per share of Revolution Medicines’ common stock exceeds 130% of the conversion price for a specified period of time and certain other conditions are satisfied. The redemption price will be equal to the principal amount of the notes to be redeemed, plus accrued and unpaid interest, if any, to, but excluding, the redemption date.

If a "fundamental change" (as defined in the indenture for the notes) occurs, then, subject to a limited exception, noteholders may require Revolution Medicines to repurchase their notes for cash. The repurchase price will be equal to the principal amount of the notes to be repurchased, plus accrued and unpaid interest, if any, to, but excluding, the fundamental change repurchase date.

Revolution Medicines estimates that the aggregate net proceeds from the offerings were approximately $2,137.2 million, after deducting the underwriting discounts and commissions and estimated offering expenses. Revolution Medicines intends to use the net proceeds from the offerings for general corporate purposes, including research and development expenses, expenses relating to the potential commercialization of one or more of its product candidates, general and administrative expenses and capital expenditures.

The offerings were made pursuant to an effective shelf registration statement on file with the Securities and Exchange Commission (the "SEC"). Each offering was made only by means of a prospectus supplement relating to that offering and an accompanying prospectus. Copies of the final prospectus supplement and the accompanying prospectus relating to each offering may be obtained for free by visiting EDGAR on the SEC’s website at www.sec.gov. Alternatively, copies of these documents may be obtained by contacting: J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717 or by email at [email protected] and [email protected]; TD Securities (USA) LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by email at [email protected]; and Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Avenue, 8th Floor, New York, NY 10017, by telephone at (212) 518-9544, or by email at [email protected].

This press release shall not constitute an offer to sell or a solicitation of an offer to buy any securities referred to in this press release, nor shall there be any sale of any such securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or other jurisdiction.

(Press release, Revolution Medicines, APR 17, 2026, View Source [SID1234664474])

On April 17, 2026 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported the presentation of multiple poster presentations at the 2026 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting highlighting the potential of rinzimetostat (ORIC-944), a potent and selective allosteric inhibitor of PRC2 to treat prostate cancer. The posters can be found in the publication section of ORIC’s website here.

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"Our research continues to show the therapeutic potential of PRC2 inhibition across the prostate cancer disease spectrum, by reducing tumor adaptability and sustaining the benefit derived from androgen-receptor targeted therapies," said Lori Friedman, PhD, chief scientific officer. "Additionally, our preclinical studies reveal that targeting PRC2 via EED has potential advantages over targeting EZH2, which, together with the clinical data generated to date, furthers our conviction that rinzimetostat is a potential best-in-class PRC2 inhibitor."

Poster presentations:

Rinzimetostat blockade of PRC2 activity, a key mechanism of treatment resistance, improves response of androgen receptor pathway inhibition across a spectrum of prostate cancer models

Key findings of the presentation:

In a transcriptomics analysis of >1,100 prostate samples spanning normal prostate, primary prostate cancer, and metastatic disease, PRC2 activity was observed early in the development of prostate cancer and was sustained during disease progression and treatment resistance, highlighting it as a critical therapeutic target.
More than half of localized primary tumors demonstrated elevated PRC2 activity vs. normal prostate tissue, and an elevated PRC2 activity in locally advanced tumors associates with poor survival, indicative of a key role early in the disease.
Elevated PRC2 activity was observed in the vast majority of both metastatic CSPC and metastatic CRPC tumors relative to normal prostate tissue.
Rinzimetostat in combination with darolutamide demonstrated antitumor activity across a breadth of in vivo models representing the prostate cancer continuum, including CSPC and CRPC.

Rinzimetostat, an allosteric EED inhibitor with best-in-class properties for the treatment of prostate cancer, is effective in PRC2 methyltransferase-resistant settings in preclinical studies

Key findings of the presentation:

PRC2 inhibition induces transcriptional and chromatin effects that restrain tumor plasticity and enhance antitumor activity of androgen receptor inhibitors in prostate cancer models.
Differential potency of PRC2 inhibitors on EZH1- vs. EZH2-containing complexes impacts activity in resistance contexts, providing potential advantages for EED targeting.
Rinzimetostat retained antitumor activity in prostate cancer cells with overexpressed EZH1 in vitro, while potency was diminished for mevrometostat or tazemetostat.
Preclinical studies show that rinzimetostat overcomes acquired resistance mechanisms observed in the clinic for tazemetostat and valemetostat.
Rinzimetostat demonstrates improved solubility, oral bioavailability, CYP profile, and clinical half-life versus comparator compounds.

(Press release, ORIC Pharmaceuticals, APR 17, 2026, View Source [SID1234664473])