On September 24, 2024 Generate:Biomedicines ("Generate") reported a multi-target collaboration with Novartis (NYSE: NVS) to discover and develop protein therapeutics across multiple disease areas (Press release, Generate Biomedicines, SEP 24, 2024, https://generatebiomedicines.com/media-center/generatebiomedicines-announces-multi-target-collaboration-with-novartis [SID1234650142]). The collaboration leverages Generate’s proprietary generative AI platform, ​"The Generate Platform," to create potentially first- and best-in-class molecules through AI-based optimization and de novo generation.

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The collaboration will combine The Generate Platform, which integrates machine learning with high-throughput experimental validation, with Novartis expertise and capabilities in target biology, biologics development, and clinical development to create novel therapeutics and to accelerate the pace of drug discovery and development.

"We are delighted to collaborate with Generate to explore the promise of generative AI in enhancing and accelerating the discovery of next-generation biologics," said Fiona Marshall, President of Biomedical Research at Novartis. ​"This collaboration offers an opportunity to leverage the unique strengths of our respective companies, from target biology and biologics discovery to machine learning/​AI and clinical development, in order to bring forward new medicines with transformative potential for patients."

"Partnering with a world-leading drug discovery and development organization like Novartis allows us to broaden the use of our cutting-edge generative biology platform to tackle even more areas of unmet medical need," said Mike Nally, Chief Executive Officer of Generate:Biomedicines. ​"We look forward to working closely with the team at Novartis to continue to demonstrate the transformative potential of programming biology to create better medicines for patients, faster."

Under the terms of the collaboration agreement, Generate will receive a total upfront payment of $65 million in cash from Novartis, which includes $15 million for the purchase of equity in Generate. Generate is also eligible to receive more than $1 billion in performance-based milestone payments, in addition to tiered royalties up to low double-digits. The number of targets and therapeutic areas are not being disclosed.

On September 24, 2024 Convergent Therapeutics Inc., a clinical stage biotechnology company focused on developing next generation radiopharmaceutical therapies for the treatment of prostate cancer and other cancers, reported that the first patient has been dosed with CONV01-α in the Phase II CONVERGE-01 trial evaluating CONV01-α, Ac-225 rosopatamab tetraxetan, for the treatment of patients with prostate-specific membrane antigen (PSMA) PET-positive metastatic castration resistant prostate cancer (mCRPC) (Press release, Convergent Therapeutics, SEP 24, 2024, View Source [SID1234646847]).

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Previously conducted academic studies of CONV01-α have shown encouraging therapeutic results in patients with prostate cancer. According to Neil Bander, MD, Convergent’s Co-founder and CSO, "In patients treated at Weill Cornell Medicine, CONV01-α demonstrated a prostate-specific antigen decline of 50% (PSA50) in 67% of patients and a PSA decline of 90% (PSA90) in 27% of patients." These results have prompted initiation of the CONVERGE-01 trial under Convergent’s own Investigational New Drug License (IND). "We look forward to evaluating the full potential of CONV01-α and advancing the Phase II trial in the months ahead."

The CONVERGE-01 trial is a Phase II, randomized, open-label, multicenter three-part study designed to assess the safety and efficacy of CONV01-α in patients with mCRPC. In Part 1, the first 5 participants will receive In-111-rosopatamab tetraxetan to characterize the biodistribution of the radioantibody to target organs and prostate cancer lesions. Participants will then be enrolled in either Part 2 (dose optimization) or Part 3 (dose escalation) depending on their prior treatment history. Part 2 will enroll Lu-177-PSMA-radioligand therapy-naïve participants and Part 3 will enroll participants who received prior Lu-177-PSMA-radioligand therapy. All patients will receive Ac-225 rosopatamab tetraxetan in a single fractionated two-week cycle. Further details of the trial can be found at www.clinicaltrials.gov under NCT identifier: NCT06549465.

Chief Medical Officer Appointment

Convergent announced that Richard Messmann, MD, MHS, MSc, has joined the company as Chief Medical Officer. Dr. Messmann is a medical oncologist and biochemist with over 25 years of experience in oncology drug development, including responsibility for the global clinical development and successful regulatory submission of Pluvicto and Locametz for the treatment of men with PSMA-expressing, mCRPC. Dr. Messmann has held leadership positions at Endocyte, Advanced Accelerator Applications (a subsidiary of Novartis), Fusion Pharmaceuticals, Amgen, Eli Lilly & Co., and others.

Immediately prior to joining Convergent Therapeutics, Dr. Messmann was the Senior Vice President and clinical lead for Fusion’s development of the actinium radiotherapeutic FPI-2265. While at Amgen, he was the executive medical director and global program lead for the development of xaluritamig (AMG 509) in prostate cancer.

"We are excited to welcome Dr. Messmann to the Convergent team as we expand our clinical program for CONV01-α," said Convergent’s Co-founder and CEO, Philip Kantoff, MD. "His deep knowledge and experience in oncology drug development, specifically leading the late-stage development of radiopharmaceuticals, is an important addition to our team as we look forward to progressing this asset forward."

Series A Extension Funding

Convergent announced a $40 million Series A extension by Novo Holdings, a holding and investment company wholly owned by the Novo Nordisk Foundation. This additional funding increases the total Series A raise to $130 million to support the development of Convergent’s radiopharmaceutical pipeline, including CONV01-α. Jim Trenkle, PhD, Partner in the Venture Investments group at Novo Holdings, joins the Convergent Board of Directors.

About CONV01-α
CONV01-α, Convergent’s alpha emitting radioantibody, combines the precision and pharmacokinetics of antibodies with the tumor-killing potential of alpha emitting radionuclides. Specifically, CONV01-α uses a humanized monoclonal antibody targeting prostate-specific membrane antigen (PSMA) which is highly overexpressed in prostate cancer cells. Since PSMA is a validated target, several therapeutics are directed at this antigen and CONV01-α is differentiated by its use of both an antibody and alpha emitter. CONV01-α is linked to a powerful radionuclide called 225Ac, which releases alpha particles which kill cancer cells through DNA double strand breaks. Unlike other radioactive sources, alpha particles deliver high-energy radiation over very short distances, thereby minimizing radiation exposure to healthy neighboring cells and tissues. Pairing highly selective antibodies with such a powerful yet precise payload offers the ideal combination to treat many types of cancers.

On September 24, 2024 Nona Biosciences, a global biotechnology company providing a total solution from "Idea to IND" (I to I ), reported that it has entered into a strategic collaboration with Alkyon Therapeutics, Inc. (AlkyonTx), a San Diego-based biotechnology company, to develop next-generation immunotherapy and other targeted therapy applications, using Nona’s Harbour Mice fully human antibody platform (Press release, Nona Biosciences, SEP 24, 2024, View Source [SID1234646848]).

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Nona Biosciences’ proprietary Harbour Mice platform has extensive potential for generating both conventional and novel heavy chain only (HCAb) antibodies that are fully human, affinity matured with excellent solubility and developability, enhancing the efficacy and precision of advanced therapies. The technology is clinically validated, globally patent protected, and worldwide endorsed and recognized.

"We are excited to partner with Alkyon Therapeutics and support their efforts to harness the power of big data in drug discovery," said Dr. Jingsong Wang, Chairman of Nona Biosciences. "This agreement underscores our dedication to leveraging our world-leading antibody discovery technologies in diverse applications to accelerate oncology drug development and enhance translatability to the clinic."

"At Alkyon, we are eager to work with Nona Biosciences, utilizing their Harbour Mice platform to advance our immunotherapy research," said Dr. Benjamin Titz, Co-Founder of Alkyon Therapeutics, Inc. "By leveraging its proprietary platform to generate deep insights into the tumor microenvironment—particularly the extracellular matrix (ECM) and stroma—Alkyon uncovers novel therapeutic targets with enhanced translational potential, accelerating the development of breakthrough treatments for solid cancers."

On September 24, 2024 Astellas Pharma Inc. (TSE:4503, President and CEO: Naoki Okamura, "Astellas") reported that Japan’s Ministry of Health, Labour and Welfare (MHLW) has approved PADCEV (enfortumab vedotin [genetical recombination]) with MSD’s KEYTRUDA (pembrolizumab [genetical recombination]) as a combination therapy for the first-line treatment of adult patients with radically unresectable urothelial carcinoma (Press release, Astellas, SEP 24, 2024, View Source,-Labour-and-Welfare-Approves-PADCEV-TM-enfortumab-vedotin-with-KEYTRUDA-R-pembrolizumab-for-First-Line-Treatment-of-Radically-Unresectable-Urothelial-Carcinoma [SID1234646833]). This is the first approved combination treatment for radically unresectable urothelial cancer in Japan to offer an alternative to platinum-containing chemotherapy, the current standard of care for first-line treatment.

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In Japan, bladder cancer is the 9th most common cancer, with over 34,500 new cases diagnosed and 11,000 deaths reported from the disease in 2022.3 Particularly poor outcomes are associated with the latter stages of the disease, with global five-year survival rates of 39% and 8% for locally advanced and metastatic urothelial cancer, respectively.4

The approval by the MHLW was supported by results from the Phase 3 EV-302 clinical trial (also known as KEYNOTE-A39) which explored the efficacy and safety of enfortumab vedotin in combination with pembrolizumab in patients with previously untreated locally advanced or metastatic urothelial cancer (la/mUC). Results showed that the treatment combination resulted in a median overall survival of 31.5 months (95% CI: 25.4-NR) compared to 16.1 months (95% CI: 13.9-18.3) with platinum-containing chemotherapy, representing a 53% reduction in risk of death (Hazard Ratio [HR]=0.47; 95% Confidence Interval [CI]: 0.38-0.58; P<0.00001). The median progression-free survival of 12.5 months (95% CI: 10.4-16.6) with the combination compared to 6.3 months (95% CI: 6.2-6.5) with chemotherapy represents a 55% reduction in the risk of cancer progression or death (HR=0.45; 95% CI: (0.38-0.54); P<0.00001). The safety results in EV-302 are consistent with those previously reported for this combination in EV-103 in cisplatin-ineligible patients with la/mUC. The most common (≥3%) Grade 3 or higher adverse events (AEs) related to treatment with enfortumab vedotin in combination with pembrolizumab were maculo-papular rash, hyperglycemia, neutropenia, peripheral sensory neuropathy, diarrhea, and anemia. No new safety issues were identified. During the EV-302 trial, approximately 30% of patients completed treatment with chemotherapy and then went on to receive maintenance therapy with avelumab, a PD-L1 inhibitor, which is reflective of current real world clinical practice.1 Results were presented at the 2023 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress and published in the New England Journal of Medicine.1

Ahsan Arozullah, M.D., M.P.H., Senior Vice President, Head of Oncology Development, Astellas
"Today’s approval by Japan’s MHLW expands the benefits of treatment with enfortumab vedotin in combination with pembrolizumab to patients living with radically unresectable urothelial carcinoma in Japan. These patients will now have an alternative to platinum-containing chemotherapy to treat this devastating disease, helping to improve patient outcomes, extend lives and give further hope to the patients and families that we serve."

In addition to this latest approval, enfortumab vedotin in combination with pembrolizumab was approved by the European Commission in August 2024 for the first-line treatment of adult patients with unresectable or metastatic urothelial cancer, who are eligible for platinum-containing chemotherapy. Furthermore, in December 2023, the U.S. Food and Drug Administration approved the use of the combination therapy for adult patients with locally advanced or metastatic urothelial cancer.

Astellas has already reflected the impact from the approval for enfortumab vedotin in Japan in its financial forecast for the current fiscal year ending March 31, 2025.

About EV-302
The EV-302 trial is an open-label, randomized, controlled Phase 3 study, evaluating enfortumab vedotin in combination with pembrolizumab versus platinum-containing chemotherapy in patients with previously untreated la/mUC. The study enrolled 886 patients with previously untreated la/mUC who were eligible for cisplatin- or carboplatin-containing chemotherapy regardless of PD-L1 status. Patients were randomized to receive either enfortumab vedotin in combination with pembrolizumab or platinum-containing chemotherapy. The dual primary endpoints of this trial are OS and PFS per RECIST v1.1 by blinded independent central review (BICR). Select secondary endpoints include ORR per RECIST v1.1 by BICR, DOR per RECIST v1.1 by BICR, and safety.1

The EV-302 trial is part of an extensive clinical program evaluating this combination in multiple stages of urothelial cancer and other solid tumors. Findings from EV-302 were presented at the 2023 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress and published in the New England Journal of Medicine.1

About Bladder and Urothelial Cancer
Urothelial cancer, or bladder cancer, begins in the urothelial cells, which line the urethra, bladder, ureters, renal pelvis, and some other organs.5 Urothelial cancer accounts for 90% of global bladder cancers and can also be found in the renal pelvis, ureter, and urethra.6,7 If bladder cancer has spread to surrounding organs or muscles, it is called locally advanced disease.8 If the cancer has spread to other parts of the body, it is called metastatic disease.9 Globally, approximately 12% of cases are locally advanced or metastatic urothelial cancer at diagnosis.10

About PADCEV (enfortumab vedotin [genetical recombination])
PADCEV (enfortumab vedotin [genetical recombination]) is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.11,12 Non-clinical data suggest the anticancer activity of enfortumab vedotin is due to its binding to Nectin-4-expressing cells, followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).11

PADCEV is indicated in Japan as monotherapy for the treatment of adult patients with radically unresectable urothelial carcinoma that has progressed after anti-cancer chemotherapy, and in combination with KEYTRUDA (pembrolizumab) for the first-line treatment of adult patients with radically unresectable urothelial carcinoma.13

Ongoing Investigational Trials
EV-302 (NCT04223856) is an open-label, randomized, controlled Phase 3 trial, evaluating enfortumab vedotin in combination with pembrolizumab versus platinum-containing chemotherapy in patients with previously untreated locally advanced or metastatic urothelial cancer (la/mUC) who were eligible for cisplatin- or carboplatin-containing chemotherapy regardless of PD-L1 status.

EV-103 (NCT03288545) is an ongoing, multi-cohort, open-label, multicenter Phase 1b/2 trial investigating enfortumab vedotin alone or in combination with pembrolizumab and/or chemotherapy in first- or second-line settings in patients with la/mUC and in patients with muscle-invasive bladder cancer (MIBC).

Enfortumab vedotin in combination with pembrolizumab is being investigated in an extensive program in multiple stages of urothelial cancer, including two Phase 3 clinical trials in MIBC in EV-304 (NCT04700124, also known as KEYNOTE-B15) and EV-303 (NCT03924895, also known as KEYNOTE-905). The use of enfortumab vedotin in combination with pembrolizumab in second-line urothelial cancer and MIBC has not been proven safe or effective.

EV-203 (NCT04995419) is a Phase 2, multicenter, single-arm bridging trial in China designed to evaluate the efficacy, safety, and pharmacokinetic performance of enfortumab vedotin as treatment for patients in China. A total of 40 patients were enrolled in the trial.

EV-104 (NCT05014139) is a Phase 1 trial exploring enfortumab vedotin in patients with non-muscle invasive bladder cancer (NMIBC). The trial will be conducted in two-parts, assessing dose escalation and dose expansion with enfortumab vedotin when administered intravesically as a monotherapy.

EV-202 (NCT04225117) is an ongoing, multi-cohort, open-label, multicenter Phase 2 trial investigating enfortumab vedotin alone in patients with previously treated advanced solid tumors. This trial also has a cohort that is investigating enfortumab vedotin in combination with pembrolizumab in patients with previously untreated recurrent / metastatic head and neck squamous cell carcinoma.

Important Safety Information
For important Safety Information for PADCEV, please see the Package Insert.

On September 24, 2024 Anixa Biosciences, Inc. ("Anixa" or the "Company") (NASDAQ: ANIX), a biotechnology company focused on the treatment and prevention of cancer, reported its strategic plan for a Phase 2 study for its breast cancer vaccine (Press release, Anixa Biosciences, SEP 24, 2024, View Source [SID1234646849]). The Phase 1 trial is being conducted at Cleveland Clinic, funded by a grant from the U.S. Department of Defense.

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The proposed Phase 2 trial will evaluate the efficacy of the vaccine administered in the neoadjuvant (before surgery) setting, in combination with chemotherapy and Keytruda (pembrolizumab). The goal of neoadjuvant therapy is to reduce tumor burden and to prevent tumor recurrence with the intent to improve survival. This clinical trial approach allows Anixa to enroll a broader range of patients, encompassing multiple types of breast cancer. The therapeutic market for breast cancer is large due to the increase in prevalence of breast cancer and an increase in screening resulting in a demand for treatment. Compared with primary prevention, the development path for breast cancer treatment is expected to have a shorter path to approval. The therapeutic market covers all stages of breast cancer, from early to advanced and metastatic cases. In 2023, the market was valued at approximately $38.35 billion and is projected to reach $89.67 billion by 2030, growing at a compound annual growth rate (CAGR) of 12.9% (Maximize Market Research).

The key objectives of the trial include evaluating the immunological response to the vaccine and comparing clinical efficacy of standard of care therapy alone with the vaccine plus standard of care therapy. A key component of this trial will be the evaluation of breast cancer tissue and the validation of the immunological mechanism of action of the vaccine.

The trial is expected to commence in 2025 and is projected to last approximately two to three years. Immunological responses to the vaccine will be made available as the trial advances, providing a faster and more cost-effective path toward potential approval and/or partnerships with pharmaceutical companies.

"We are excited to unveil our Phase 2 study plan, bringing us one step closer to a potentially transformative therapy for breast cancer patients," said Dr. Amit Kumar, Chairman and CEO of Anixa Biosciences. "By targeting treatment rather than prevention, we can reach a broader patient population and potentially expedite the process of regulatory approval and partnerships. This trial marks a key milestone in advancing our mission to fight cancer through innovative therapies. While our Phase 2 trial focuses on the therapeutic market, with the data obtained in this trial, we expect to conduct additional, more informed studies for both recurrence prevention and primary prevention with partners in the future."

Initial Phase 1 data was presented at the San Antonio Breast Cancer Symposium in December 2023. The data showed no safety concerns, with protocol defined immune responses observed in a majority of patients. Additional data from the Phase 1 trial will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in early November 2024.

The Phase 1 trial is conducted in collaboration with Cleveland Clinic and is funded by a grant from the U.S. Department of Defense. Anixa is the exclusive worldwide licensee of the novel breast cancer vaccine technology developed at Cleveland Clinic. The grant funding from the U.S. Department of Defense was provided to Cleveland Clinic.