On January 16, 2025 Alligator Bioscience (Nasdaq Stockholm: ATORX) reported the positive outcome of regulatory interactions with the Paul Ehrlich Institute (PEI) of Germany and the US Food and Drug Administration (FDA) regarding the CMC development of mitazalimab, which is in development as a first-line treatment for metastatic pancreatic cancer in combination with mFOLFIRINOX (Press release, Alligator Bioscience, JAN 16, 2025, View Source [SID1234649755]).

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A recent Type C CMC interaction with the FDA in December 2024 reinforced feedback received from the PEI in July 2024, confirming that the completed and planned CMC work through early 2025 enables the Phase 3 development of mitazalimab. With this feedback, Alligator initiated manufacturing of mitazalimab to be used in the Phase 3 study, and thus remains on track for initiation of Phase 3 clinical activities during 2025.

"This regulatory feedback from both the FDA and PEI demonstrates the robustness of our CMC development strategy and validates the significant progress we’ve made in advancing mitazalimab towards Phase 3" said Søren Bregenholt, CEO of Alligator Bioscience. "We are confident in our ability to continue to execute on our timeline and bring mitazalimab one step closer to addressing the urgent unmet need for patients with metastatic pancreatic cancer."

PHYRAGO Represents the First and Only Improved Version of SPRYCEL That Can Be Safely Co-administered With Gastric Acid-Reducing Agents

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On January 15, 2025 Handa Pharmaceuticals, Inc. ("Handa") (6620.TWO) announced that its U.S. subsidiary, Handa Therapeutics, LLC (the "Company"), has acquired PHYRAGO (dasatinib) tablets, a U.S. Food and Drug Administration ("FDA") approved chronic myeloid leukemia treatment that was developed by Nanocopoeia, LLC (Press release, Nanocopoeia, JAN 15, 2025, View Source [SID1234650016]). PHYRAGO is the first and only dasatinib product that can be co-administered with gastric acid-reducing agents. An estimated one-third of patients who require SPRYCEL treatment may also take gastric acid-reducing agents1, which can reduce dasatinib’s drug exposure by more than 40% when taken with a proton pump inhibitor and more than 60% when taken with an H2 receptor antagonist2.

PHYRAGO was granted Orphan-Drug Designation and has received three (3) years of data exclusivity that will expire December 5, 2026. Should PHYRAGO be granted Orphan-Drug Exclusivity, it may be eligible for seven (7) years of exclusivity, until December 5, 2030. PHYRAGO is protected by several issued patents, including those listed in the FDA’s Approved Drugs and Therapeutic Equivalents publication (the "Orange Book") that expire January 22, 2041.

The Company is in the process of selecting a U.S. commercialization partner and expects PHYRAGO to be available to patients in Q1-2025.

PHYRAGO is indicated for adult patients with newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase and adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) who no longer benefit from, or did not tolerate, other treatments.

"PHYRAGO represents a novel dasatinib formulation that delivers equivalent efficacy to SPRYCEL, with the additional benefit of allowing patients to take dasatinib with gastric acid-reducing agents", said Bill Liu, Chairman and CEO of Handa. "Unlike SPRYCEL, PHYRAGO allows concomitant use with a proton pump inhibitor or H2 receptor antagonist."

The effect of co-administration of gastric acid-reducing agents on SPRYCEL is significant. The SPRYCEL label warns that the "co-administration of SPRYCEL with a gastric acid-reducing agent may decrease the concentration of dasatinib. Decreased dasatinib concentrations may reduce efficacy. Do not administer H2 agonists or proton pump inhibitors with SPRYCEL."3

The FDA approved PHYRAGO with a label that allows co-administration with gastric acid-reducing agents, stating that "No clinically significant differences in the pharmacokinetics of PHYRAGO were observed following concomitant use with omeprazole (proton pump inhibitor) or famotidine (H2 receptor antagonist)."4 and "Avoid concomitant use of PHYRAGO with antacids. If concomitant use of an antacid cannot be avoided, administer the antacid at least 2 hours prior to or 2 hours after the dose of PHYRAGO."5

According to Bristol Myers Squibb’s annual report, net sales of SPRYCEL in 2023 totaled $1.44 billion. For full prescribing information about PHYRAGO, please visit www.phyrago.com.

Sources:

IQVIA longitudinal prescription and medical claims data, January 2013-March 2021, identified 7,419 patients receiving dasatinib treatment of which 31.8% were concomitantly prescribed a proton pump inhibitor and/or H2 receptor antagonist
SPRYCEL Prescribing Information (Rev. 7/2024), Section 12.3, Pharmacokinetics – Drug Interaction Studies – Gastric Acid Reducing Agents
SPRYCEL Prescribing Information (Rev. 7/2024), Section 7.1, Drug Interactions – Effect of Other Drugs on Dasatinib – Gastric Acid Reducing Agents
PHYRAGO Prescribing Information (Rev. 12/2024), Section 12.3, Pharmacokinetics – Drug Interaction Studies – Gastric Acid Reducing Agents
PHYRAGO Prescribing Information (Rev. 12/2024), Section 2.2, Dosage Modifications – Antacids

On January 15, 2025 Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) reported positive topline results from the China subpopulation of the global Phase 3 innovaTV 301 study, demonstrating a clinically meaningful improvement in overall survival with TIVDAK treatment for patients with previously treated recurrent or metastatic cervical cancer compared to chemotherapy (Press release, Zai Laboratory, JAN 15, 2025, View Source [SID1234649751]).

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The China subpopulation results were consistent with those in the global population:

TIVDAK demonstrated a 45% reduction in the risk of death compared to chemotherapy (HR: 0.55 [95% CI: 0.27-1.15] in the China subpopulation who had received prior standard systemic therapies, with more than half of this Chinese population having received prior anti-PD(L)1 therapy. Median OS for patients treated with TIVDAK was not reached versus chemotherapy 10.7 months [95% CI: 6.0-not reached] with a median follow-up of 11.5 months.
Secondary endpoints of PFS and confirmed ORR also favored treatment with TIVDAK compared to chemotherapy.
The safety profile of TIVDAK in the China subpopulation was manageable and consistent with the global profile.
"Recurrent or metastatic cervical cancer remains a significant challenge for patients, highlighting a critical unmet need for effective treatments that extend survival after relapse," said Dr. Rafael Amado, M.D., President, Head of Global Research and Development at Zai Lab. "The consistent and positive results in the China subpopulation of the global Phase 3 study reinforce the potential for TIVDAK, the only ADC therapy in this disease setting, to increase options in this therapeutically unmet clinical setting. If approved, we expect TIVDAK to add to ZEJULA and augment our commercial franchise in women’s tumors."

"There are approximately 150,000 new cases of cervical cancer annually in China1, and patients face limited treatment options once their cancer recurs or spreads after initial treatment," said Dr. Lingying Wu, Professor of the Department of Gynecologic Oncology of National Cancer Center / Cancer Hospital Chinese Academy of Medical Sciences. "While the recent adoption of immunotherapy as a first-line treatment in China represents progress, there is a lack of effective options for patients following relapse. The promising results from TIVDAK, which demonstrated superior survival extension in patients whose disease progressed after initial treatments, including prior anti-PD(L)1 treatment, offer hope for addressing this critical unmet need."

In April 2024, the U.S. Food and Drug Administration (FDA) approved the supplemental Biologics License Application (sBLA) granting full approval for TIVDAK (tisotumab vedotin-tftv) for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. The approval was based on results from the global, randomized, Phase 3 innovaTV 301 clinical trial (NCT04697628), which met its primary endpoint, demonstrating overall survival (OS) benefit in adult patients with previously treated recurrent or metastatic cervical cancer treated with TIVDAK compared to chemotherapy.

TIVDAK demonstrated a 30% reduction in the risk of death compared to chemotherapy (hazard ratio [HR]: 0.70 [95% CI: 0.54-0.89], two-sided p=0.0038)2. Median OS for patients treated with TIVDAK was 11.5 months [95% CI: 9.8-14.9] versus chemotherapy 9.5 months [95% CI: 7.9-10.7].
PFS and confirmed ORR were also significantly improved compared to chemotherapy.
The safety profile of TIVDAK was consistent with its known safety profile as presented in the U.S. prescribing information, and no new safety signals were observed.
Based on these encouraging results, Zai Lab intends to submit an NDA for TIVDAK to China’s National Medical Products Administration (NMPA) in the first quarter of 2025. The full China subpopulation data will be presented at a future medical conference in 2025.

About innovaTV 301 Trial Design

The innovaTV 301 trial (NCT04697628) is a global, 1:1 randomized, open-label Phase 3 trial evaluating TIVDAK (tisotumab vedotin) versus investigator’s choice of single agent chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) with recurrent or metastatic cervical cancer who received chemotherapy.

Patients with recurrent or metastatic cervical cancer with squamous cell, adenocarcinoma, or adenosquamous histology, and disease progression during or after treatment with chemotherapy doublet +/- bevacizumab and an anti-PD-(L)1 agent (if eligible) are included. The primary endpoint was overall survival. The main secondary outcomes were progression-free survival and objective response rate.

The study was conducted by Seagen, which was acquired by Pfizer in December 2023, in collaboration with Genmab, European Network of Gynaecological Oncological Trial Groups (ENGOT, study number ENGOT cx-12) and the Gynecologic Oncology Group (GOG) Foundation (study number GOG 3057), as well as other global gynecological oncology cooperative groups.

For more information about the Phase 3 innovaTV 301 clinical trial and other clinical trials with tisotumab vedotin, please visit www.clinicaltrials.gov.

About Cervical Cancer in China

Cervical cancer remains one of the leading causes of cancer death in women in China and globally. An estimated 150,000 new cases of cervical cancer occur annually in China1. Current treatment options are limited for patients with recurrent or metastatic cervical cancer with disease progression on or after systemic therapy. TIVDAK is well positioned to provide a new option for previously treated advanced cervical cancer patients who currently have limited treatment options and poor outcomes.

About TIVDAK (tisotumab vedotin)

TIVDAK (tisotumab vedotin) is an antibody-drug conjugate (ADC) composed of Genmab’s human monoclonal antibody directed to tissue factor (TF) and Pfizer’s ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody. Nonclinical data suggest that the anticancer activity of tisotumab vedotin is due to the binding of the ADC to TF-expressing cancer cells, followed by internalization of the ADC-TF complex, and release of MMAE via proteolytic cleavage. MMAE disrupts the microtubule network of actively dividing cells, leading to cell cycle arrest and apoptotic cell death. In vitro, tisotumab vedotin also mediates antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity.

TIVDAK received accelerated approval from the FDA in September 2021 and full approval in April 2024 for adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.

Please see full prescribing information, including BOXED WARNING for TIVDAK here.

Zai Lab has an exclusive license from Seagen Inc., a company later acquired by Pfizer, to develop and commercialize TIVDAK in Greater China (mainland China, Hong Kong, Macau, and Taiwan, collectively).

On January 15, 2025 OS Therapies, Inc. (NYSE-A: OSTX), a clinical-stage biotechnology company advancing immunotherapies and targeted drug conjugates for cancer treatment, reported positive data from a Phase 2b clinical trial (NCT04974008) of OST-HER2 (OST31-164) – the Company’s HER2-targeted immunotherapy candidate in the rare pediatric-designated indication of prevention of recurrent, fully resected, lung metastatic osteosarcoma (Press release, OS Therapies, JAN 15, 2025, View Source [SID1234649750]). The data demonstrate statistically significant results in the primary endpoint of the study, 12-month event free survival (‘EFS’), where an event is defined as the recurrence of metastatic osteosarcoma, in OST-HER2-treated patients when compared with the leading published historical comparable control group. Further as of the most recent follow up, the data show a strong trend in favor of OST-HER2-treated patients in overall survival (‘OS’, remaining alive) at the 1-year and 2-year interim timepoints of the ongoing 3-year overall survival secondary endpoint. Notably, all patients who achieved the primary 12-month EFS endpoint remain alive.

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"We are extremely pleased with these results of our Phase 2b clinical trial because they show that OST-HER2-treated patients achieved the primary endpoint of 12-month EFS in a statistically significantly higher ratio than comparable historical controls, in addition to increasing the likelihood of 1-year and 2-year survival as compared with comparable historical controls," commented Dr. Robert Petit, Chief Medical & Scientific Officer of OS Therapies. "The strong safety profile shown in this study also supports the use of OST-HER2 in this incredibly difficult-to-treat population that has no currently approved therapies."

"The achievement of the primary endpoint in the OST-HER2 phase 2b is a tremendous success that opens the possibility, for the first time, of meaningful therapy for patients suffering from osteosarcoma with lung metastases after resection. This is a leap forward in the development of OST-HER2 and we are pleased that our regulatory strategy is consistent with the FDA’s recent draft guidance update for accelerated approvals. With these positive data in hand, we are preparing to engage with U.S. FDA on an accelerated pathway for approval in this extremely challenging indication," said Paul Romness, MHP, Chair & CEO of OS Therapies. "We do not expect to have to treat additional patients as part of this process with FDA."

Phase 2b Clinical Trial Data

Enrollment Criteria:

12-39 years old
Recurred, fully resected lung only metastatic (METS) Osteosarcoma
39 evaluable patients at 21 centers, single treatment arm
52 Weeks on Study: Dosed 16 times every 3 weeks for 48 weeks with 4-week follow-up final visit
Primary Endpoint of 12-month EFS:

33% for OST-HER2 vs. 20% for historical control1 (p = 0.0158)
Interim Analysis of Ongoing Secondary Endpoint, OS:

1-year OS: 91% for OST-HER2 vs. 80% for historical control2 (p = 0.0700)
2-year OS: 61% for OST-HER2 vs. 40% for historical control2 (p = 0.0576)
Post-Hoc Analyses

12-months EFS Subgroup Analysis in the OST-HER2 Treatment Group:

Gender (Males vs Females), n = 39:

Females (n=19) = 47%
Males (n= 20) = 20%
(p= 0.0604)
Number of lung resections (1 Prior Resection vs. 2+ Prior Resections), n= 39:

1 Prior Resection (n= 28) = 25%
2+ Prior Resections (n= 11) = 55%
(p = 0.1366)
12-month EFS Responders using a Non-Concurrent Control Group from the only existing US osteosarcoma database with patients qualified for disease-free status following a fully-resected lung-only metastasis of osteosarcoma origin:

OST-HER2, n=39
12-month EFS Responders = 13/39 (33%)
NCCG, n=9
12-month EFS Responders = 1/9 (11%)
(p = 0.1848)
Time to recurrence in patients who did not achieve 12-month EFS:

OST-HER2, n=26 = 5.9 months
NCCG, n=8 = 4.7 months
(p = 0.1454)
About OST-HER2

OST-HER2 is an innovative immunotherapy using a HER2 bioengineered form of the bacteria Listeria monocytogenes (Lm) to trigger a strong immune response against cancer cells expressing HER2. This off-the-shelf immunotherapy treatment is designed to prevent metastasis, delay recurrence, kill primary tumors expressing HER2 alone and potentially in combination with existing approved therapies, and increase overall survival. OST-HER2 has received Rare Pediatric Disease Designation (RPDD) from the FDA and Fast Track and Orphan Drug Designations from the FDA and European Medicines Agency (EMA).

The US FDA granted OST-HER2 rare pediatric disease designation for osteosarcoma in 2021. The US FDA rare pediatric disease PRV program aims to incentivize drug development for rare pediatric diseases. Under this voucher program, a sponsor who receives an approval for a drug or biological product for a rare pediatric disease qualifies for a voucher that can be redeemed to receive priority review for a different product. The sponsor may also transfer or sell the voucher to another sponsor. OS Therapies intends to sell the PRV it would earn upon receiving an approval of OST-HER2 for recurrent, fully resected, lung metastatic osteosarcoma. The most recent publicly disclosed sale price of a PRV was on November 27th, 2024 when PTC Therapeutics announced selling its PRV to Kebilidi for $150M. With emerging scarcity in the PRV market, the Company expects the value of PRVs to increase going forward. The maximum sale price of a PRV was in 2015 when AbbVie bought a priority review voucher from United Therapeutics for $350 million.

The most recent continuing resolution (CR) negotiations in the US House of Representatives failed to reauthorize the PRV program for pediatric cancers such as osteosarcoma. Despite this, as a result of OS Therapies’ having been granted OST-HER2’s rare pediatric disease designation prior to December 20, 2024 in addition to the Company’s aim to receive an approval for OST-HER2 in the rare pediatric disease osteosarcoma in 2025, prior to the September 30, 2026 deadline, OS Therapies remains eligible to receive the PRV upon approval of OST-HER2 in recurrent, resected metastatic osteosarcoma.

The osteosarcoma treatment market was estimated at $1.2 billion in 2022 according to Data Bridge Market Research. Approximately 50% of patients are diagnosed with a lung metastasis at some point following surgical resection and chemotherapy. 3-year survival rates in patients who were not diagnosed with a metastasis are 59%. 3-year survival rates in patients who were diagnosed with pulmonary metastasis were 30%. The Company believes the market opportunity for OST-HER2 in the prevention of lung metastases is over $500 million.

On January 15, 2025 Chromatin Bioscience reported its ongoing collaboration with EsoBiotec, which has successfully advanced its ESO-T01 in vivo CAR-T candidate into clinical trials (Press release, EsoBiotec, JAN 15, 2025, View Source [SID1234649749]). ESO-T01 is the first in vivo B-cell maturation antigen (BCMA) CAR-T candidate to reach the clinical stage and utilises a synthetic promoter designed using Chromatin Bio’s proprietary promoter design platform, chromatinLENS, exclusively for EsoBiotec as part of its innovative approach to immunotherapy.

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EsoBiotec’s ESO-T01, developed using its ENaBL platform, is a T cell targeted lentiviral vector expressing a BCMA-targeted CAR construct for the treatment of multiple myeloma. This construct is regulated by a Treg-specific synthetic promoter developed in collaboration with Chromatin Bioscience. Early studies demonstrated highly effective in vivo transduction, with the BCMA CAR transgene expressed specifically in T cells, leading to the generation of a large population of circulating BCMA CAR-T cells that persisted throughout the study. These results highlight the long-term durability and efficacy of the engineered T cells, marking an important milestone for the therapeutic.

"ESO-T01 is the first in vivo BCMA CAR-T candidate to advance to the clinical stage, showcasing the capabilities of our ENaBL platform technology that reprograms immune cells within the body to combat cancer," stated EsoBiotec CEO Jean-Pierre Latere, Ph.D. "While various treatments exist for multiple myeloma, including ex vivo CAR-T options, many come with severe side effects and are limited by manufacturing capacity, logistical challenges, and high costs. We are excited to collaborate with Chromatin Bioscience to integrate this innovative synthetic promoter, aiming to enhance the safety and efficacy profile of ESO-T01."

Chromatin Bioscience’s chromatinLENS platform allows for the identification of highly specific, cell-type selective gene regulatory elements from the dark genome, offering significant advantages in minimising off-target effects while ensuring robust and durable therapeutic efficacy. These promoters are critical in ensuring the success of advanced therapies like ESO-T01, where targeted expression in T cells is paramount for the safety and efficacy of the treatment.

"EsoBiotec’s progress to the clinic is an exciting development in the field of gene therapy," said Michael Roberts, CEO and Founder of Chromatin Bioscience. "Our synthetic promoters are designed to provide precision and durability in gene expression, and we are pleased that they are playing a role in ensuring the success of ESO-T01. This collaboration represents the power of combining cutting-edge gene therapy with targeted gene expression technologies to offer new treatment options for patients."