On December 14, 2022 Ellipses Pharma ("Ellipses"), a global drug development company focused on accelerating the development of new oncology treatments, reported the first dosing of a patient in EP0031-101, a trial investigating Ellipses’ next generation selective RET inhibitor (SRI) EP0031 (Press release, Ellipses Pharma, DEC 14, 2022, View Source [SID1234625287]).

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EP0031 is an SRI which aims to address the unmet need for patients with RET-altered tumours (Non-Small Cell Lung Cancer (NSCLC), medullary thyroid and other RET-altered tumours) who have progressed on first generation SRIs. This global, modular, Phase 1/2 trial will evaluate the safety, tolerability and efficacy of EP0031 in patients with advanced RET-altered tumours and is now open to enrolment at multiple US sites. Ellipses plans to open further trial sites in the UK and EU in 2023.

Developed in partnership with Sichuan Kelun-Biotech Pharmaceutical Co., Ltd (Kelun-Biotech), EP0031, known as A400 when in conjunction with Kelun-Biotech’s ongoing regional development, is already under clinical investigation in China for NSCLC and thyroid cancers. Kelun-Biotech continues to rapidly progress their clinical trial which is now in the dose expansion stage. Kelun will present clinical data for the first time at an international conference in 2023.

Prof Tobi Arkenau, Global Head of Drug Development & CMO, commented:

"Enrolment has started at UCLA, Portland Providence, MD Anderson and University of Kentucky and these will be joined by more sites in the next few months. There is an increasing number of patients whose cancers progress despite treatment with first generation SRIs, and as such EP0031 provides an exciting opportunity to address this unmet need."

Dr Rajan Jethwa, Chief Executive Officer & Founder of Ellipses, commented:

"EP0031 is a promising next generation SRI that seeks to address some of the issues with first generation SRIs. Dosing the first patient in this trial is an important first step for EP0031. Next generation SRIs offer the potential to expand the armamentarium against RET-driven cancers and further improve patient outcomes."

Dr Junyou Ge, Chief Executive Officer of Kelun-Biotech, commented:

"A400 (EP0031) offers a significant therapeutic potential for tumours with RET oncogene mutation/fusion and is hoped to bring new treatment options for patients. We are pleased that the EP0031-101 trial has dosed the first patient in the United States and congratulate our partner Ellipses on this important milestone. Kelun-Biotech will continue to collaborate with Ellipses to promote the global development and subsequent potential commercialisation of A400 to benefit more cancer patients around the world."

About EP0031 (A400)

EP0031 is a potent next generation SRI with broad activity against common RET fusions and mutations, including solvent front resistance mutations. Therefore, EP0031 (A400) may have the potential to overcome resistance to first generation SRIs. An IND application for EP0031 (A400) was approved by China’s National Medicinal Products Administration (NMPA) in June 2021 and a Phase 1/2 trial is ongoing in China. In March 2021, Kelun-Biotech granted Ellipses an exclusive license for EP0031 (A400) in certain territories including the US and Europe, with Kelun-Biotech retaining certain rights in Greater China and part of the Asia-Pacific region. In June 2022, the US FDA approved the EP0031 IND application, and the Ellipses Phase 1/2 trial is ongoing in the US.

About RET-altered cancers

It is estimated that RET fusions & mutations may be responsible for ≃2% of all cancers, this includes 2% of NSCLC, 60-80% of medullary thyroid cancers (MTC) and <1-20% across a range of other cancers.1 When patients progress on currently approved first generation SRIs there are limited treatment options and prognosis is poor.

On December 14, 2022 -CatalYm reported three major expansions of its ongoing Phase 2 visugromab clinical development program. Based on initial positive patient responses, the company is advancing two potential lead indication cohorts into the second stage of the Simon-2-stage design ahead of schedule (Press release, Catalym, DEC 14, 2022, View Source [SID1234625286]). Additionally, CatalYm is expanding its visugromab Phase 2 development program to include a new confirmatory cohort exploring the response-predictive biomarkers identified in the Phase 1.

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The Phase 2 study is evaluating visugromab in advanced-stage cancer patients that are relapsed or refractory to prior anti-PD-1/-PD-L1 treatment in a selected group of solid tumor indications. Based on early emerging responses in several major solid tumor indications, Catalym will enlarge the Phase 2 by expanding two cohorts as foreseen in the Phase 2 protocol. The persuasive responses seen in the study to date enable the expansion earlier than anticipated and before the original cohorts were fully enrolled. Combined with the clinical data generated in the Phase 1, these data further support the significant potential of visugromab in this PD-1 refractory solid tumor patient population.

In addition, CatalYm expanded its Phase 2 study with a newly established, tumor-agnostic, fully biomarker-selected cohort. This cohort aims to assess the prediction accuracy of response for two potential biomarkers in a total of 25 cancer patients treated with the GDF-15-targeting antibody visugromab in combination with the anti-PD1 antibody nivolumab in patients that are relapsed/refractory to prior anti-PD1/PD-L1 treatment. The two biomarkers were identified as part of the company’s stringent Phase 1 biomarker program where triple-biopsies were mandatory and evaluated regarding molecular and immunohistochemical parameters of significance. The company recently presented mature results from this Phase 1 dose escalation study at the 2022 ESMO (Free ESMO Whitepaper) congress.

"Our first indication-specific cohorts reaching the trigger for stage-2 enrolment before having completed enrolment of stage 1 is a clearly positive signal for the clinical potential of visugromab in advanced-stage, anti-PD1/PD-L1 relapsed/refractory cancer patients. In light of the highly promising phase 1 biomarker data, we now also added a fully biomarker-selected cohort to our program, to ideally confirm these early findings. This progress in the development of visugromab is exciting to see." stated Prof. Dr. Eugen Leo, Chief Medical Officer at CatalYm. "Identifying biomarkers that predict treatment outcomes is a critical endeavor in modern cancer medicine. The ability to identify the patients that will benefit most is a highly valuable additional asset for the future development of visugromab."

Dr. Phil L’Huillier, Chief Executive Officer at CatalYm added: "We have set up this Phase 2 program to confirm the potential clinical benefit of targeting GDF-15 in specific solid tumor indications. The new biomarker cohort and the first Simon-2-stage expansions will help us to gather valuable information for the future development of visugromab and should bring us significantly closer to registration trials. We are highly encouraged by the clear development opportunities unfolding in front of us which have also been validated through our recent oversubscribed Series C funding. Our path toward rapidly bringing this novel IO therapy to cancer patients is clear."

Recruitment for the biomarker expansion cohort has been initiated in Spain, Germany and Switzerland as part of the ongoing multi-center, open-label, GDFATHER-2 trial (NCT04725474). The Phase 2 part of the study, originally commenced in February 2022, is evaluating the treatment of GDF-15 neutralizing antibody, visugromab, in combination with the anti-PD-1 checkpoint inhibitor nivolumab in advanced stage cancer patients that are relapsed or refractory to prior anti-PD-1/-PD-L1 treatment. The study is planned to enroll up to 164 participants aged 18 years or older in up to 7 cohorts at major clinical centers across Europe and the United States. The biomarker-selected cohort will include broad tissue analyses, incorporating protein- and RNA-levels as well as analysis of the patient’s tumor immunogram which will be correlated with clinical outcomes. An initial data update from the first cohorts of the study is expected in mid 2023. CatalYm recently completed a €50 million Series C funding round to support the continued late-stage development of the program.

On December 14, 2022 Precision Biologics, Inc. ("Precision"), a clinical-stage immunotherapy and targeted oncology company, reported the successful completion of the safety phase and the enrollment of new patients into the expansion of the Phase 2 Clinical Trial Combining Precision Biologics NEO-201 monoclonal antibody with Pembrolizumab (Keytruda) (Press release, Precision Biologics, DEC 14, 2022, View Source [SID1234625285]).

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The study is enrolling patients at the National Cancer Institute, part of the National Institutes of Health, Bethesda, MD, with metastatic Non-Small Cell Lung Cancer (NSCLC), Head and Neck Cancers, Endometrial Cancer and Cervical Cancer, who have already been treated with checkpoint inhibitor therapy (including prior Keytruda). (View Source)

This ongoing Phase 2 trial is testing to see if the combining of NEO-201 with Keytruda can reactivate the killing activity once checkpoint inhibitors no longer work alone.

Christina M Annunziata, MD, PhD, Clinical Director of the Women’s Malignancy Branch at the NCI has been working both preclinically and overseeing this ongoing clinical trial.

"In our laboratory, we have been studying how this antibody can be used in various cancer treatments. Based on the main mechanisms of action, we have moved forward with a phase 2 clinical trial in combination with pembrolizumab," said Dr. Annunziata.

NEO-201 is a unique monoclonal antibody with multiple mechanisms of action. It has been shown previously to kill cancer cells expressing its target. Additionally, it has been shown in early clinical trials to reduce immune suppressive cells that may be responsible in diminishing cancer killing activity for drugs like Keytruda.

On December 14, 2022 Zymeworks Inc. (NYSE: ZYME), a clinical-stage biopharmaceutical company developing multifunctional biotherapeutics, reported the upcoming presentation of mature Phase 2 data evaluating zanidatamab in combination with chemotherapy as first-line treatment for HER2-positive gastroesophageal adenocarcinoma (GEA) at the ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium, taking place in San Francisco, CA and virtually on January 19-21, 2023 (Press release, Zymeworks, DEC 14, 2022, View Source [SID1234625284]).

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The GEA cohort of this Phase 2 clinical trial (NCT03929666) was fully recruited as of March 1, 2022 with clinical trial sites in the United States, Canada, Chile and South Korea. Enrollment into the biliary tract cancer and colorectal cancer cohorts of the trial continues. The Phase 2 data in GEA supports zanidatamab development in the Phase 3 HERIZON-GEA-01 study, evaluating zanidatamab in combination with chemotherapy with or without tislelizumab for the first-line treatment of HER2-positive GEA (NCT05152147).

The poster presentation will be available on Thursday, January 19, 2023 on the conference website as well as the Zymeworks website.

Title: Zanidatamab + chemotherapy as first-line treatment for HER2-expressing metastatic gastroesophageal adenocarcinoma (mGEA)
Lead Author: Elena Elimova, MD, MSc, Princess Margaret Cancer Center, Toronto, Canada
Abstract: 347
Poster Session A: Cancers of the Esophagus and Stomach and Other GI Cancers

About Zanidatamab

Zanidatamab is a bispecific antibody, based on Zymeworks’ Azymetric platform, that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design results in multiple mechanisms of action including dual HER2 signal blockade, increased binding and removal of HER2 protein from the cell surface, and potent effector function leading to encouraging antitumor activity in patients. Zymeworks is developing zanidatamab in multiple Phase 1, Phase 2 and pivotal clinical trials globally as a targeted treatment option for patients with solid tumors that express HER2. Zymeworks has entered into separate agreements with each of BeiGene, Ltd. (BeiGene) and Jazz Pharmaceuticals Ireland Limited (Jazz), granting each of BeiGene and Jazz with exclusive rights to develop and commercial zanidatamab throughout various counties around world.

On December 14, 2022 Alpha-9 Theranostics Inc., a clinical stage company developing differentiated and highly targeted radiopharmaceuticals with the potential to meaningfully improve the treatment of people living with cancer, reported an oversubscribed $75 million Series B financing (Press release, Alpha-9 Theranostics, DEC 14, 2022, View Source [SID1234625282]). The round was led by Nextech Invest, with participation from Frazier Life Sciences, Samsara BioCapital and Quark Venture in addition to existing investors Longitude Capital and BVF Partners.

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Alpha-9 is engineering highly effective, bespoke radiopharmaceuticals for the treatment of solid and hematologic malignancies. These molecules are optimized to selectively deliver radiation to tumor sites while minimizing off-target effects. The Series B funding will support advancement of the company’s five programs into the clinic over the next two years while expanding its early-stage programs.

"We have always believed in the company, its founders, and the potential for radiotherapies to effectively address a wide range of cancers," said David Hirsch, M.D., Ph.D., Chief Executive Officer of Alpha-9. "Our team has done excellent work progressing our pipeline of novel radiopharmaceuticals over the last year, and we are excited to have the support of these top-tier investors. With this new investor partnership, we are well positioned to progress multiple targets into the clinic, harnessing the potential of radiopharmaceuticals to realize more effective treatments for people living with cancer."

Alpha-9’s systematic approach to radiotherapeutic design is fueled by a toolbox of technologies and chemistries, which offers broad potential for expansion into a multitude of oncology targets. Leveraging its founders’ deep expertise in the modification of peptides and small molecules, Alpha-9 tailors each component of its radiopharmaceuticals – binder, linker, chelator and radioisotope – to improve the molecule’s overall performance. The company’s development process includes human imaging and dosimetry studies, which provide early feedback on molecule design. This approach is capital efficient and rapid, resulting in de-risked compounds prior to later-stage clinical evaluation.

"The radiopharmaceutical field has evolved over the past several years, attributable to scientific advances, translational data and strong clinical efficacy," said Melissa McCracken, Ph.D., Partner at Nextech Invest and Alpha-9 Board member. "This new generation of radiopharmaceuticals shows improved tumor uptake with limited off-target exposure, resulting in drugs that have better safety and efficacy profiles in the clinic. We are excited by the progress Alpha-9 has demonstrated and are proud to support expansion of its programs and facilities."

In addition to advancing the clinical pipeline, the Series B will enable Alpha-9 to grow its team to support discovery programs. Furthermore, the company will complete the build-out of its research facilities in Vancouver, BC, which will house the chemistry, biology, translational research and radiochemistry teams, as well as support product formulation. Alpha-9 has also invested in radioisotope supply through agreements with multiple lutetium and actinium partners. The company looks forward to expanding these relationships with the Series B proceeds.

The company, headquartered in both Boston and Vancouver, was founded in 2019 by François Bénard, M.D., Kuo-Shyan Lin, Ph.D., and David Perrin, Ph.D., leading researchers from BC Cancer and the University of British Columbia with deep expertise in the modification of peptides and small-molecules to create novel radiopharmaceuticals.

Melissa McCracken, Ph.D., Partner at Nextech Invest, Patrick Heron, M.B.A., Managing Partner at Frazier Life Sciences, Cory Freedland, Ph.D., Partner at Samsara BioCapital, and Matthew Young, M.B.A., Managing Director at Longitude Capital will join the Alpha-9 Board of Directors, along with Darcy Mootz, Ph.D., Site Head at Amunix, a Sanofi Company (Chief Business Officer prior to sale), who will join as a Board advisor.