On January 4, 2024 Avenzo Therapeutics, Inc. (Avenzo), a clinical-stage biotechnology company developing next generation oncology therapeutics, reported that it has entered into an exclusive licensing agreement with Allorion Therapeutics Inc. (Allorion) to develop and commercialize AVZO-021 (formerly ARTS-021), a potentially best-in-class cyclin-dependent kinase 2 (CDK2) selective inhibitor globally (excluding Greater China) (Press release, Avenzo Therapeutics, JAN 4, 2024, View Source [SID1234638991]). As part of the agreement, Avenzo also receives an exclusive option for an additional preclinical program planned for IND submission in early 2025.

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CDK2 has emerged as a promising target given its role as a resistance mechanism to approved CDK4/6 therapies in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer, and given its role as an oncogene in many cyclin E1 (CCNE1) amplified cancers. Avenzo will leverage its internal drug development expertise to advance AVZO-021, which is currently being studied in a Phase 1 clinical trial across multiple sites in the U.S. for the treatment of HR+/HER2- metastatic breast cancer and other advanced solid tumors.

"With this agreement, we have laid the foundation for our potentially best-in-class oncology pipeline," said Athena Countouriotis, M.D., co-founder, president and CEO of Avenzo. "Patients with HR+/HER2- metastatic breast cancer continue to have limited therapeutic options, and we believe AVZO-021 may provide patients with a new treatment option both as a single agent and in multiple combinations. We are excited to advance the ongoing Phase 1 clinical study (NCT05867251), and to partner with the Allorion team to advance the program globally."

Under the terms of the license agreement, Allorion will receive an upfront payment of $40 million and be eligible to receive additional payments based on achievement of certain development, regulatory and commercial milestones and tiered royalties on net sales by Avenzo. Potential payments for both programs may total more than $1 billion.

"We developed AVZO-021 as a potential best-in-class CDK2-selective inhibitor to address an area of unmet medical need," said Peter Ding, co-founder and CEO of Allorion. "The Avenzo team has a proven track record and deep expertise in developing and advancing next-generation oncology therapies. We are delighted to partner with Avenzo to drive innovation and transform the treatment landscape for cancer patients."

"AVZO-021 is a highly potent and selective CDK2 inhibitor for the treatment of HR+/HER2- breast cancer and CCNE1-amplified cancers," said Afshin Dowlati, M.D., Professor of Medicine and Oncology at University Hospitals Seidman Cancer Center and Case Western Reserve, and Director of the Early Phase Therapeutics Program. "I look forward to working with Avenzo as they continue to develop this therapy that has the potential to provide a new treatment option to patients fighting cancer."

In preclinical studies, AVZO-021 exhibited nanomolar potency against CDK2 while sparing other CDKs with high selectivity over CDK1, a key driver of toxicity. In addition, AVZO-021 demonstrated efficacy in in vivo xenograft models, both as a single agent and in combination with CDK4/6 inhibitors. Allorion disclosed select data in poster presentations at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) in October 2023.

On January 4, 2024 OnCusp Therapeutics, Inc., a biopharmaceutical company dedicated to transforming cutting-edge preclinical innovation into clinically validated treatments for cancer patients worldwide, reported an oversubscribed $100 million Series A financing round (Press release, OnCusp Therapeutics, JAN 4, 2024, View Source [SID1234638990]).

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The round was co-led by Novo Holdings, OrbiMed, and F-Prime Capital, alongside Sofinnova Investments, Catalio Capital Management, Marshall Wace, Forge Life Science Partners, Blackbird BioVentures, CJNV BioVenture and others, as well as BioTrack Capital, a co-lead for the Seed Round. OnCusp Therapeutics has raised $139 million since its establishment in April 2021. The proceeds from this financing will be used to advance CUSP06, an ADC targeting CDH6, toward clinical proof-of-concept. Additionally, the capital will aid in expanding the OnCusp portfolio and team.

CUSP06 has strong preclinical data demonstrating the potential for best-in-class activity. Engineered to increase potency, heighten "bystander effect," elevate linker stability, and overcome drug resistance, CUSP06’s differentiating attributes could translate into higher clinical response rates and durability, with an improved safety profile. Having obtained FDA IND clearance in 3Q 2023, CUSP06 will be in a first-in-human Phase I study in the US.

"We are grateful to have the trust and support from some of the most prominent global biotech investors," said Dr. Bing Yuan, Co-Founder and CEO of OnCusp Therapeutics. "I am also thankful to the OnCusp team for their commitment and excellent work. We hold a strong conviction to develop innovative oncology therapies for patients. This significant Series A financing enables OnCusp to accelerate the development of CUSP06 and other game-changing therapeutics in our fight against cancer."

As part of the financing, OnCusp Therapeutics will appoint Dr. Karen Hong, Partner in the Venture Investments team at Novo Holdings US, Inc., a wholly owned subsidiary of Novo Holdings; Diyong Xu, Principal at OrbiMed; and Dr. Chong Xu, Partner at F-Prime Capital, to the company’s Board of Directors.

"We are thrilled to have co-led this round. The remarkable progress that the company has made in such a short time is a testament to its highly efficient business model and the team’s exceptional execution capabilities," said Dr. Karen Hong. "We share OnCusp’s mission in bringing oncology innovations to life and are committed to supporting the company’s continued growth and success."

"ADCs have become one of the most promising modalities for treating cancer, and CDH6 is emerging as a winning ADC target. We believe CUSP06 is well positioned to unlock the full potential of this target, both in high and low CDH6 expressing tumors," said Diyong Xu. "We also look forward to OnCusp expanding its portfolio to fully leverage its translational and clinical development expertise."

"I am excited to join the OnCusp Board at this transformative moment for the company," stated Dr. Chong Xu. "F-Prime is committed to proactively champion breakthrough approaches like CUSP06, which holds immense potential to help patients with ovarian cancer and other advanced solid tumors. I look forward to working with other board members and the executive team to propel OnCusp to its next phase of growth."

"As a major investor since the company’s inception, I am impressed by the entrepreneurship, commitment, and perseverance exemplified by the OnCusp team in the current challenging biotech market." added Dr. Jiacong Guo, one of OnCusp’s current Board Directors and a Principal at BioTrack Capital. "I believe companies who are leading their field will emerge triumphant in their mission. I am confident that OnCusp is one of those companies."

On January 4, 2024 JW Therapeutics (HKEx: 2126), an independent and innovative biotechnology company focusing on developing, manufacturing and commercializing cell immunotherapy products, reported that the National Medical Products Administration (NMPA) of China accepted the supplemental Biological License Application (sBLA) for its anti-CD19 autologous chimeric antigen receptor T (CAR-T) cell immunotherapy product Carteyva (relmacabtagene autoleucel injection) for the treatment of adult patients with relapsed or refractory Mantle Cell Lymphoma (r/r MCL) (Press release, JW Therapeutics, JAN 4, 2024, View Source [SID1234638989]). This is the third marketing application on Carteyva submitted by JW Therapeutics, and is expected to be the first cell therapy product approved in China for the treatment of patients r/r MCL. Carteyva was granted, by NMPA, Breakthrough Therapy Designation in Mar 2022, as well as Priority Review in Dec. 2023.

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MCL is a rare and heterogeneous B cell non-Hodgkin lymphoma which is currently incurable with existing therapies[1]. MCL, associated with a poor prognosis, mainly occurs in elderly men who were not diagnosed until advanced stage[2]. Significant progress has been made in the last decade as the treatment paradigm has shifted from traditional chemoimmunotherapy toward targeted therapies such as bruton tyrosine kinase inhibitors (BTKi). Despite the use of BTKi in r/r MCL has improved their survival outcomes, many patients will ultimately relapse with shortened remission durations (6~10 months) [3]. Notwithstanding the above, there are still unmet medical needs for a safe, effective novel approach to overcome the limitations of current treatments of r/r MCL.

The sBLA was supported by the clinical results from a single-arm, multi-center, pivotal study on Carteyva in adult participants with r/r MCL in China. In the study, participants with r/r MCL who had been treated with a CD20-targeting antibody, anthracycline or bendamustine, or BTKis were included. After being treated with lymphodepleting chemotherapy, participants received relma-cel (100×106 CAR+ T cells). As of Oct 25, 2023, a total of 59 participants received relma-cel infusion. Of 56 efficacy evaluable participants, relma-cel demonstrated remarkable clinical responses achieving high rates of objective response rate (ORR) and complete response rate (CRR) (3 months best ORR 81.36%, 3 months best CRR 66.10%) and the incidence of severe (grade ≥ 3) cytokine release syndrome (CRS) was 6.8%, the incidence of severe (grade ≥ 3) neurotoxicity (NT) was 6.8%.

Mark J. Gilbert, MD, Chief Medical Officer of JW Therapeutics, noted: "We are delighted to have a product that can deliver meaningful efficacy in this disease, nearly 70% of participants with r/r MCL have achieved complete remission after treatment with relma-cel, and the overall safety data demonstrated that the treatment was generally well tolerate. Carteyva is expected to become the first commercial CAR-T cell product for the treatment of r/r MCL in China."

On January 4, 2024 AbbVie (NYSE: ABBV), and Umoja Biopharma (Umoja), an early clinical-stage biotechnology company, reported two exclusive option and license agreements to develop multiple in-situ generated CAR-T cell therapy candidates in oncology using Umoja’s proprietary VivoVecTM platform (Press release, AbbVie, JAN 4, 2024, View Source [SID1234638988]). The first agreement provides AbbVie an exclusive option to license Umoja’s CD19 directed in-situ generated CAR-T cell therapy candidates. This includes UB-VV111, Umoja’s lead clinical program for hematologic malignancies currently at the IND-enabling phase. Under the terms of the second agreement, AbbVie and Umoja will develop up to four additional in-situ generated CAR-T cell therapy candidates for discovery targets selected by AbbVie.

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"As we continue to strengthen our oncology portfolio, we believe that in-situ CAR-T cell therapy represents a paradigm shift utilizing genetic medicine concepts," said Jonathon Sedgwick, Ph.D., vice president and global head of discovery research at AbbVie. "We look forward to working with Umoja’s team to advance next-generation in-situ CAR-T therapies, and potentially expand the patient populations and indications benefitting from conventional CAR-T approaches."

Umoja’s VivoVecTM gene delivery platform combines third generation lentiviral vector gene delivery with a novel T-cell targeting and activation surface complex. This enables T cells in the body to manufacture their own cancer-fighting CAR-T cells in vivo. This has the potential to eliminate a number of challenges associated with traditional CAR-T approaches including reliance on gathering a patient’s own or donor cells which are modified externally before being delivered back to the patient, the associated time lag and manufacturing challenges of ex vivo cell modification, and the need for patient’s lymphodepletion.

"AbbVie is an ideal partner for Umoja given their broad expertise in development and commercialization of novel therapeutics in hematology, oncology, and beyond," said David Fontana, Ph.D., chief operating and business officer at Umoja.

"By bringing together AbbVie’s like-minded pursuit of addressing patient unmet needs with our investments in vector biology and fully-owned commercial-scale manufacturing, we look forward to progressing multiple VivoVec drug candidates into the clinic in the coming years," added Andrew Scharenberg, M.D., co-founder and chief executive officer at Umoja.

Under the terms of the two agreements, Umoja received upfront payments and an equity investment from AbbVie. Additionally, for the two agreements combined, Umoja may be eligible to receive up to $1.44B in aggregate for option exercise fees, development and regulatory milestones, with the potential for Umoja to earn additional sales-based milestones and tiered royalties on worldwide net sales.

On January 4, 2024 The Menarini Group ("Menarini"), a leading international pharmaceutical and diagnostics company, and Stemline Therapeutics, Inc. ("Stemline"), a wholly-owned subsidiary of the Menarini Group focused on bringing transformational oncology treatments to cancer patients, along with clinical stage generative artificial intelligence (AI)-driven biotechnology company Insilico Medicine ("Insilico"), reported that they have entered into an exclusive licensing agreement granting Stemline the global rights to develop and commercialize a novel, small molecule KAT6A inhibitor designed using Insilico’s AI platform, as a potential treatment for hormone sensitive cancers and other oncology indications (Press release, Menarini, JAN 4, 2024, View Source [SID1234638987]).

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Breast cancer is the most commonly diagnosed tumor type and the leading cause of cancer death among women, globally.[1] Approximately 70% of breast cancers are estrogen receptor positive (ER+), and endocrine therapy remains the backbone of therapy for patients with ER+ breast cancer. However, tumors can develop a resistance to endocrine therapy, which in turn can lead to disease progression. This is a significant clinical challenge and highlights the urgent need for novel therapies to help overcome treatment resistance.

KAT6A is known to play an important role in several cancers. Overexpression of KAT6A correlates with poor clinical outcomes in patients with ER+/HER2- breast cancer, the most common subtype of breast cancer. In preclinical studies, the molecule has demonstrated potent inhibition against KAT6A in multiple CDX and PDX models with good efficacy and safety. Insilico presented data on the molecule at the San Antonio Breast Cancer Symposium in early December.

"We are delighted to enter a collaboration with Insilico that harnesses the power of generative AI as a leader in the field, to explore a promising new treatment approach and potentially unlock transformative new cancer therapies," said Elcin Barker Ergun, CEO of the Menarini Group. "Having brought the first innovation in endocrine therapy after almost 20 years to the U.S. and Europe with elacestrant for ER+, HER2- breast cancer patients, our aim is to further augment patient outcomes, and targeting KAT6A can potentially serve that in breast cancer and beyond."

The novel molecule was designed by Insilico’s R&D team with the help of its end-to-end Pharma Generative AI platform to inhibit KAT6A and block endocrine receptor (ER) at the transcriptional level, giving it the potential to overcome resistance to endocrine therapies due to mutation or ligand-independent constitutive activation of ER. Currently, endocrine therapy in combination with CDK4/6 inhibitors is the standard treatment for ER+/HER2- breast cancer patients with advanced or metastatic disease. Novel combinations with CDK4/6 inhibitors and/or new oral SERDs are needed to further extend outcomes.

"We are excited by the promise of our latest generative AI-designed therapy to provide a new potential treatment option for breast cancer patients," says Alex Zhavoronkov, PhD, founder and co-CEO of Insilico Medicine. "With their innovative vision and deep focus in bringing transformational therapeutics in oncology, Stemline is the ideal partner to lead this molecule into development and through clinical trials."

Under the terms of the agreement, Stemline will provide a $12 million upfront payment to Insilico. The combined value of the deal, including all development, regulatory, and commercial milestones, is over $500 million, followed by royalties up to double digits.