On May 23, 2024 Bicycle Therapeutics plc (the "Company") reported to have entered into a securities purchase agreement (the "Purchase Agreement") with the purchasers named therein (the "Investors") (Filing, 8-K, Bicycle Therapeutics, MAY 23, 2024, View Source [SID1234643578]). Pursuant to the Purchase Agreement, the Company agreed to sell an aggregate of 25,933,706 of its American Depositary Shares ("ADSs"), each representing one of the Company’s ordinary shares, nominal value £0.01 per share (the "Ordinary Shares"), and in lieu of ADSs to Investors that so choose, non-voting ordinary shares (the "Non-Voting Ordinary Shares"), each at a purchase price equal to $21.42 per share (the "Private Placement"). The Purchase Agreement contained customary representations and warranties from the Company and the Investors and customary closing conditions. The closing of the Private Placement is expected to occur on May 28, 2024 (the "Closing Date"). The Company anticipates the aggregate gross proceeds of the Private Placement will be approximately $555 million before deducting placement agent fees and other expenses.

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Pursuant to the Purchase Agreement, the Company has agreed to prepare and file a registration statement with the Securities and Exchange Commission no later than 30 calendar days following the Closing Date, or a prospectus supplement to its registration statement on Form S-3ASR (File No. 333-272248) (if such registration statement is then effective) no later than 15 business days following the Closing Date, for purposes of registering the Registrable Securities (as defined in the Purchase Agreement). The ADSs are registered on registration statements on Form F-6 (File Nos. 333-231422 and 333-279465).

The Company has also agreed, among other things, to indemnify the Investors, their officers, directors, and constituent partners, legal counsel, and each person who controls such Investors from certain liabilities and to pay certain legal fees and other expenses reasonably incurred by the Investors in connection therewith.

The foregoing description of the Purchase Agreement does not purport to be complete and is qualified in its entirety by reference to the Purchase Agreement filed as Exhibit 10.1 to this report and incorporated by reference herein.

On May 23, 2024 Arvinas, Inc. (Nasdaq: ARVN) reported that two abstracts, including one for ARV-766 in prostate cancer and one for TACTIVE-K, a Phase 1b/2 clinical trial with vepdegestrant, a novel investigational oral PROteolysis Targeting Chimera (PROTAC) ER degrader, in combination with Pfizer’s atirmociclib (PF-07220060), an investigational CDK4 inhibitor, were accepted for presentation at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Congress held May 31 to June 4, 2024, in Chicago, IL (Press release, Arvinas, MAY 23, 2024, View Source [SID1234643576]).

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Presentation details are as follows:

Title: ARV-766, a PROteolysis TArgeting Chimera (PROTAC) androgen receptor (AR) degrader, in metastatic castration-resistant prostate cancer (mCRPC): initial results of a phase 1/2 study
Presentation Type and Abstract Number: Rapid Oral Abstract, 5011
Date: Monday, June 3, 2024
Time: 1:15 p.m. — 2:45 p.m. CDT
Category: Genitourinary Cancer—Prostate, Testicular, and Penile

Title: TACTIVE-K: phase 1b/2 study of vepdegestrant, a PROteolysis TArgeting Chimera (PROTAC) estrogen receptor (ER) degrader, in combination with PF-07220060, a cyclin-dependent kinase (CDK)4 inhibitor, in ER+/human epidermal growth factor receptor 2 (HER2)- advanced breast cancer
Presentation Type and Abstract Number: Trial-in-Progress (TiP) TPS1131, Poster 103b
Date: Sunday, June 2, 2024
Time: 9:00 a.m. — 12:00 p.m. CDT
Category: Session Type and Title: Poster Session – Breast Cancer—Metastatic

Abstracts are now available via the official ASCO (Free ASCO Whitepaper) Annual Congress website here.

About ARV-766
ARV-766 is an investigational, orally bioavailable PROTAC protein degrader designed to selectively target and degrade the androgen receptor (AR). Preclinically, ARV-766 has demonstrated activity in models of wild type androgen receptor tumors in addition to tumors with AR mutations or amplification, both common potential mechanisms of resistance to currently available AR-targeted therapies.

In April 2024, Arvinas entered into a transaction with Novartis that included an exclusive license agreement for the worldwide development and commercialization of ARV-766. Closing of the transaction is subject to customary closing conditions, including the expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976.

About Vepdegestrant
Vepdegestrant is an investigational, orally bioavailable PROTAC protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of patients with ER positive human epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-) breast cancer. Vepdegestrant is being developed as a potential monotherapy and as part of combination therapy across multiple treatment settings for ER+/HER2- metastatic breast cancer.

In July 2021, Arvinas announced a global collaboration with Pfizer for the co-development and co-commercialization of vepdegestrant; Arvinas and Pfizer share worldwide development costs, commercialization expenses, and profits.

The U.S. Food and Drug Administration (FDA) has granted vepdegestrant Fast Track designation as a monotherapy in the treatment of adults with ER+/HER2- locally advanced or metastatic breast cancer previously treated with endocrine-based therapy.

On May 23, 2024 Amphista Therapeutics ("Amphista"), a leader in next generation targeted protein degradation (TPD) approaches, reported the unveiling of a new mechanism of action for the degradation of BRD9, an emerging target in oncology, that is differentiated from cereblon- or VHL-based PROTACs, during an oral presentation at the 2024 Protein Degradation in Focus Symposium held in Dundee, UK (Press release, Amphista Therapeutics, MAY 23, 2024, View Source [SID1234643575]).

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This significant news for the TPD field builds upon an earlier announcement by Amphista of two compelling data sets demonstrating in vivo efficacy and central nervous system (CNS) activity of its mechanistically differentiated protein degraders. At today’s presentation titled "Degradation of BRD9 by a novel targeted glue", Dr Andrea Testa, Scientific Co-Founder and Senior Director, Discovery Chemistry showed data from proteomic and genetic validation studies which demonstrate that Amphista’s bifunctional degraders induced degradation of BRD9 by target-assisted E3 ligase recruitment. This novel mechanism selectively induces the proximity of BRD9 to DCAF16 and serves as a molecular glue. DCAF16 is a cullin-RING E3 ligase which can facilitate degradation of proteins of interest via ternary complex formation. Induction of this complex leads to deep and rapid degradation of BRD9 in vivo.

Louise Modis, Chief Scientific Officer of Amphista Therapeutics, said: "The discovery of a novel mechanism for BRD9 degradation, differentiated from cereblon- or VHL-based PROTACs, is a testament to Amphista’s proprietary chemistry and know-how. Our ability to translate this novel approach into high-quality, drug-like compounds with oral bioavailability and activity in vivo is truly exciting. As we continue to spearhead our efforts to advance new TPD approaches, our goal remains clear – to expand the offering of TPD medicines beyond CRBN and VHL-based agents and bring effective treatments to patients in areas of high unmet need."

In the results presented, Amphista’s sub-nanomolar BRD9 degraders showed activity in both solid and liquid cancer cell lines and demonstrated a high degree of selectivity over 8,000 proteins quantified by proteomics, including the closely related proteins BRD7 and BRD4. Notably, these compounds induced BRD9 degradation in a mouse xenograft model illustrating Amphista’s BRD9 degraders are orally bioavailable and active in vivo. This is the first-time in vivo degradation of BRD9 has been demonstrated via DCAF16, underscoring the potential therapeutic application of Amphista’s bifunctional degraders.

Building on this knowledge, Amphista is applying its proprietary scientific know-how and expertise to the development of targeted glues which induce degradation of different targets, expanding the opportunity beyond BRD9. Future announcements will provide details of additional pipeline targets as part of Amphista’s ambitions to develop a first- and/or best-in-class portfolio of degraders with leading physicochemical properties.

On May 23, 2024 Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) products for cancer and autoimmune disease, reported it will participate in the TD Cowen 5th Annual Oncology Innovation Summit (Press release, Allogene, MAY 23, 2024, View Source [SID1234643571]).

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TD Cowen 5th Annual Oncology Innovation Summit
Tuesday, May 28, 2024
9:30am PT/12:30pm ET

The webcast will be posted to the Company’s website at www.allogene.com under the Investors tab in the News and Events section. Following a live webcast, a replay will be available on the Company’s website for approximately 30 days.

On May 23, 2024 Alligator Bioscience (Nasdaq Stockholm: ATORX) reported that two clinical abstracts on its lead drug candidate mitazalimab, a best-in-class CD40 agonist, in first line metastatic pancreatic cancer will be presented (abstracts 2569 and 4133) in a poster presentation session at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place in Chicago, IL and online during May 31-June 4 (Press release, Alligator Bioscience, MAY 23, 2024, View Source [SID1234643569]).

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Data presented at ASCO (Free ASCO Whitepaper) from the OPTIMIZE-1 study, of mitazalimab in combination with mFOLFIRINOX chemotherapy, showed that pharmacological analyses identified mitazalimab-induced expansion of CD4 effector T cells one week after first administration as a correlate of treatment outcomes. These data suggest the contribution of mitazalimab to tumor responses, and further supports the unique trial design of OPTIMIZE-1.

OPTIMIZE-1 achieved its primary endpoint, demonstrating a confirmed Objective Response Rate (ORR) of 40.4%, an unconfirmed ORR of 50.9% and a disease control rate (DCR) of 79% in 57 evaluable patients, as per the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). This compares favorably to the ORR of 31.6% reported in a similar patient population treated with FOLFIRINOX alone.[1] Median Duration of Response (DoR) was 12.5 months, remarkably longer than reported so far with any other approved and investigational therapies. Median Overall Survival (OS) was 14.3 months and the survival estimate from the next planned analysis may further improve.

"Most pancreatic cancer patients are diagnosed after the disease has already metastasized. Treatment options at this stage are rather unsatisfactory and there is a major need of novel therapies for these patients. The primary analysis results of OPTIMIZE-1 study suggest that adding mitazalimab to the modified FOLFIRINOX regimen significantly prolongs the durability of response, resulting in a meaningful extension of overall survival in this fatal disease. It is indeed encouraging to see many patients still continuing in the study, and we are very much looking forward to the 18-month survival follow-up from OPTIMIZE-1, which we expect at the end of June 2024," said Dr. Sumeet Ambarkhane, CMO of Alligator Bioscience. "These results support the continued development of mitazalimab in combination with mFOLFIRINOX, in a confirmatory, phase 3, clinical trial in patients with previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC). Furthermore, the correlation of mitazalimab-induced immune activation with improved clinical outcomes suggests a potential immunological profile that could be used as a biomarker for this treatment."
The open-label, multi-center OPTIMIZE-1 study assessed the safety and efficacy of mitazalimab (CD40 mAb agonist) in combination with standard of care chemotherapy mFOLFIRINOX, in previously untreated, chemotherapy naïve patients. More details can be found with the clinicaltrials.gov identifier NCT04888312.

Poster Presentations Details
Title: CD4 effector T cell expansion to identify objective responses to the CD40 agonist mitazalimab in combination with modified FOLFIRINOX (mFFX) as first-line therapy for metastatic pancreatic ductal adenocarcinoma (mPDAC) in the OPTIMIZE-1 study
Presenter: Peter Ellmark, PhD
Abstract: 2569
Track: Developmental Therapeutics—Immunotherapy
Location: Hall A | On Demand
Time: 1 June 2024, 09:00 – 12:00 (GMT-5)

Title: OPTIMIZE-1 primary analysis: Safety, efficacy and biomarker results of a phase 1b/2 study combining CD40 agonist mitazalimab with mFOLFIRINOX in previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC)
Presenter: Jean-Luc Van Laethem, MD, PhD
Abstract: 4133
Track: Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary
Location: Hall A | On Demand
Time: 1 June 2024, 13:30 – 16:30 (GMT-5)

[1] Conroy et al., N Engl J Med 2011; 364:1817-1825; DOI: 10.1056/NEJMoa1011923

About pancreatic cancer

Pancreatic cancer is the 12th largest cancer by number of patients. It is expected to become the second leading cause of cancer death in the western world by 2030. There are about 200,000 annual cases in the U.S. and the EU, with very poor prognosis: five-year survival is about 10% and median survival about 6 months. For 80% of patients, the only option is chemotherapy that offers only marginal benefit. FOLFIRINOX is expected to be the preferred first line regimen in the U.S. and the EU for patients with good performance status.