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Last patient with liver cancer included in the monotherapy part of Medivir’s phase Ib study with MIV-818

On March 25, 2021 Medivir AB (Nasdaq Stockholm: MVIR) reported that the last patient with advanced liver cancer has been included in the first part of the phase Ib study with MIV-818 (Press release, Medivir, MAR 25, 2021, View Source [SID1234577185]). Like the other patients in the study, the patient is dosed in cycles of three weeks starting with MIV-818 as monotherapy for five days. In parallel, the company is preparing part two of the phase Ib study to be able to begin during the second half of 2021.

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It is gratifying that we this far have managed to carry out the study without any major delays despite the ongoing Covid-19 pandemic. We are now preparing for the second part of the study where MIV-818 will be used as combination therapy. Details of the planned combination study will be presented during the second quarter of this year. We believe that MIV-818 has the potential to significantly improve the treatment of patients with liver cancer, said Yilmaz Mahshid, CEO of Medivir.
The first part of the phase Ib study of MIV-818 is a classic dose-escalation study with three cohorts of three patients with advanced liver cancer who have undergone previous treatments. The purpose is to further investigate the safety and tolerability profile and to determine the starting dose for part two of the phase Ib study. Data from the first part of the study is expected to be presented at a future scientific conference.

About MIV-818
MIV-818 is a pro-drug designed to selectively treat liver cancers and to minimize side effects. It has the potential to become the first liver-targeted, orally administered drug for patients with HCC and other forms of liver cancer.

About liver cancer
Liver cancer is the third leading cause of cancer-related deaths worldwide and hepatocellular carcinoma (HCC) is the most common cancer that arises in the liver. Although existing therapies for advanced HCC can extend the lives of patients, treatment benefits are insufficient and death rates remain high. HCC is a very diverse disease with multiple cancer cell types and without specific mutations seen in other tumor types. This has contributed to the lack of success of molecularly targeted agents in HCC. The limited overall benefit, taken together with the poor overall prognosis for patients with intermediate and advanced HCC, results in a large unmet medical need.

BioAtla Announces Full Year 2020 Financial Results And Provides Business Update

On March 25, 2021 BioAtla, Inc., a global clinical-stage biotechnology company focused on the development of Conditionally Active Biologic (CAB) antibody therapeutics, reported financial results for the full year 2020 and provided an update on its business (Press release, BioAtla, MAR 25, 2021, View Source [SID1234577184]).

"BioAtla made several achievements in 2020 that significantly enhance the company’s ability to advance our CAB clinical programs, expand our development portfolio, and further exploit the opportunities of our CAB technology," stated Jay M. Short, Ph.D., chairman, chief executive officer and co-founder of BioAtla, Inc. "The encouraging clinical trial data that allows us to proceed into potentially registration-enabling Phase 2 clinical trials along with prospects of developing several CAB bispecific candidates underscore the potentially broad applicability of CAB technology to address a wide range of tumor types and other indications," added Scott Smith, president of BioAtla.

Advancing clinical trials for lead candidates BA3011, BA3021 and BA3071
We are developing BA3011, CAB-AXL-ADC, as a potential therapeutic for multiple solid tumors, including soft tissue and bone sarcoma, non-small cell lung cancer (NSCLC) and ovarian cancer with other potential indications in the future. We have completed a Phase 1 trial in patients with refractory solid tumors, established a recommended Phase 2 dose, and continue to dose patients that are responding to therapy. We recently initiated dosing in a potentially registration-enabling Phase 2 clinical trial in soft tissue and bone sarcoma. We have also initiated a Phase 2 clinical trial in PD-1 refractory NSCLC patients. Additionally, we expect a multi-center investigator-initiated trial in platinum-resistant ovarian cancer will likely commence in the first half of 2021.

We are developing our second product candidate BA3021, CAB-ROR2-ADC, a CAB antibody directed against ROR2, a receptor tyrosine kinase that is overexpressed across many different solid tumors including breast, lung, pancreatic, renal, colorectal, head and neck and melanoma. We are developing BA3021 as a potential therapeutic for multiple solid tumors, including NSCLC, ovarian cancer and melanoma. We have completed a Phase 1 all-comers dose-escalation trial with BA3021 where we observed two partial responses in advanced, treatment refractory NSCLC and one partial response in melanoma which represents all ROR2 positive patients at a Phase 2 relevant dose and ROR2 expression level. We believe BA3021 has broad potential as a cancer therapy for patients with advanced solid tumors. We recently initiated Phase 2 enrollment in patients with PD-1 refractory NSCLC and melanoma.

BA3071, is a CAB anti-CTLA-4 antibody that is being developed as an immuno-oncology agent with the goal of delivering the efficacy of approved CTLA-4 antibodies, such as ipilimumab, but with lower toxicities due to the CAB’s tumor microenvironment-restricted activation. In a global collaboration with Beigene, we are developing BA3071 as a potential therapeutic for multiple solid tumor indications, including renal cell carcinoma, NSCLC, small cell lung cancer, hepatocellular carcinoma, melanoma, bladder cancer, gastric cancer and cervical cancer. BeiGene is responsible for all costs of development, manufacturing and commercialization globally. BioAtla is eligible to receive milestone payments and royalties on product sales upon regulatory approvals and commercialization by BeiGene. A Phase 1 dose-escalation trial of BA3071 as monotherapy and in combination with tislelizumab, an anti-PD-1 antibody in late stage development by BeiGene, are planned to commence in 2021.

Plans to advance development of several bispecific CAB candidates
We have also leveraged our CAB technology to develop bispecific antibodies, which bind both a tumor-specific antigen and a T cell receptor using CAB antigen-binding domains. With this design, bispecific antibodies can induce potent T cell responses against tumors expressing the tumor target antigen in a simplified manner relative to even off-the-shelf or allogeneic CAR-T therapies. We have shown in preclinical experiments that our CAB bispecific molecules meet or exceed the activity of conventional bispecifics and reduce systemic activation of potentially fatal immune responses. We advanced two CAB bispecific antibody product candidates, EpCAM/CD3 and B7-H3/CD3, into IND-enabling studies in the second half of 2020. We are also evaluating ADC modalities for each of our CAB bispecific molecules, including EGFR/CD3 and Nectin-4/CD3. Our goal is to submit up to four US INDs in 2022 for our CAB bispecific or ADC molecules.

Recent peer-reviewed publication in Proceedings of the National Academy of Sciences (PNAS) indicates potentially broad application of BioAtla’s CAB technology
The paper describes the design and functionality of therapeutic antibody candidates utilizing BioAtla’s proprietary CAB technology making them active only in the acidic tumor microenvironment while binding is reversibly inhibited in healthy tissue. This improved tumor targeting utilizes a newly discovered chemical switch system and is shown in animal models to provide for potent anti-tumor activity with markedly reduced toxicity to normal tissue, indicating a widened therapeutic index. BioAtla scientists discovered this novel chemical switch mechanism that involves physiological-occurring chemicals, such as bicarbonate and hydrogen sulfide. These molecules are negatively charged at physiological conditions and interact with positive charged areas on the protein surface. Under acidic conditions of the tumor microenvironment they are neutralized and released from the protein surface, uniquely allowing CAB antibodies to bind to their target and attack the tumor cell. BioAtla refers to this novel physiological mechanism, used for generating CABs, as Protein-associated Chemical Switch(es) or PaCS mechanism.

It is expected from the studies described in the paper that there is a potential for other yet to be identified PaCS molecules in disease related microenvironments, whether controlled through pH, concentration, or other molecular characteristics (intra- or intermolecularly) for enhancing a drug’s therapeutic index. Potential new therapeutic candidates addressing these opportunities are not limited to antibodies, but also include small molecules, encompassing lipids, sugars and nucleic acid-based agents or drugs. Further, it is expected that PaCS protein-chemical systems are important naturally occurring regulatory systems linked to a range of disease-related microenvironments, including cancer, inflammation and cellular senescence.

Full year 2020 financial results
Cash and cash equivalents as of December 31, 2020 were $238.6 million compared to $3.7 million as of December 31, 2019. In July 2020, BioAtla completed a successful private placement offering with institutional investors, for net proceeds of approximately $68.2 million. In December 2020, we received net proceeds of approximately $198.4 million from our initial public offering. We expect current cash and cash equivalents will be sufficient to fund planned operations at least through end of 2022.

Research and development (R&D) expenses were $19.9 million for the full year ended December 31, 2020 compared to $25.9 million for the year 2019. We expect our R&D expenses to increase substantially for the foreseeable future as we continue to invest in R&D activities to advance our product candidates, and our clinical programs and expand our product candidate pipeline.

General and administrative (G&A) expenses were $10.6 million for the full year ended December 31, 2020 compared to $7.5 million for the year 2019. We expect our G&A expenses to increase as a result of operating as a public company. In addition, we expect our intellectual property expenses to increase as we expand our intellectual property portfolio.

Net loss for the full year ended December 31, 2020 was $35.9 million compared to a net loss of $29.8 million for the year 2019.

Isotopia Molecular Imaging and Molecular Targeting Technologies have signed a clinical supply agreement for Lu177 n.c.a.

On March 25, 2021 Isotopia Molecular Imaging reported that it has begun a collaboration with Molecular Targeting Technologies, Inc. (MTTI), a clinical stage biopharmaceutical company, for the supply of the medical radioisotope no-carrier-added 177Lu (n.c.a. 177Lu) to support clinical development of its targeted radiotherapeutic products (Press release, Isotopia Molecular Imaging, MAR 25, 2021, View Source [SID1234577183]).

Molecular Targeting Technologies, Inc. (MTTI) has received an exclusive worldwide license from the National Institutes of Health to commercialize targeted radiotherapeutics covered by their Evans Blue (EB) platform technology patents.177Lu-EBTATE, which targets somatostatin receptors type 2 (SSTR2) in a variety of neuroendocrine tumors (NETs), and 177Lu-EBRGD for integrin expressing cancers in Glioblastoma multiforme (GBM) and Non-Small Cell Lung cancer (NSCLC), are the first products in development. In this breakthrough, EB is affixed to the targeting peptide radiopharmaceutical. That combination binds reversibly to circulating serum albumin, enhancing radiotherapeutic circulation half-life and delivering higher accumulation to targeted tumors.

177Lu is a beta-emitting radiopharmaceutical precursor with a half-life of 6.7 days and a maximum energy of 0.5 MeV, corresponding to a maximum soft-tissue penetration of approximately 1 mm from its binding site. 177Lu is used in Precision Oncology for Targeted Radionuclide Therapy. It, precisely, destroys the tumor when bound to disease-specific, targeting therapeutics. Isotopia has developed a unique, stable, consistent and reliable GMP method to produce a highly pure form of 177Lu. n.c.a. Isotopia’s 177Lu contains no metastable 177mLu, eliminating cost intensive clinical waste management.

Isotopia’s CEO Dr. Eli Shalom stated, "Our strategy is to be partner to every leading pharmaceutical company developing Lu-177 n.c.a based products, supporting them from clinical trials through commercial sale. We are committed to produce 52 weeks per year, ensuring supply through long-term contracts. We’re patient-centric. Our two years of robust, reliable and flawless production enhances patient confidence. MTTI is a remarkable company which advances their vision for the development of new radiotherapeutics and Isotopia is proud to be part of it."

Dr. Chris Pak, MTTI’s President & CEO said, "We’ve secured a timely and sustainable supply of a key therapeutic ingredient needed for the development and launch of our lead asset 177Lu-EBTATE and other EB platform technologies. We are excited to start this collaboration and build what promises to be a great relationship with a reliable and trusted radioisotope supply partner like Isotopia for the purest form of 177Lu-177 n.c.a."

Antengene Appoints Kevin Lynch as Chief Medical Officer

On March 25, 2021 Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative biopharmaceutical company dedicated to discovering, developing, and commercializing global first-in-class and/or best-in-class therapeutics in hematology and oncology, reported the appointment of Kevin Lynch, M.D. as Chief Medical Officer (CMO) of Antengene (Press release, Antengene, MAR 25, 2021, View Source [SID1234577182]). In this position, Kevin will be responsible for the strategy, direction, and execution of the company’s clinical development plans and will directly report to Dr. Jay Mei, Founder, Chairman and CEO of Antengene.

Kevin has almost 30 years of experience in R&D in the pharmaceutical industry. He has experience in multiple national, regional and global clinical roles, building organizations across Clinical Development and Medical Affairs previously at Novartis and Celgene. At Celgene, he was Vice President leading the European Clinical Development program before his most recent role in Asia-Pacific as Vice President and Head of Clinical Development and Medical Affairs.

Kevin has led all phases of clinical development across numerous novel therapies to commercial launch and post-registration development. Moreover, he has been closely involved in the clinical development of multiple transformational cancer therapies, including Glivec, Tasigna, Zometa, Femara, Revlimid, Pomalyst, and Vidaza.

"The foundation of Antengene is a remarkable story and a great tribute to Dr. Jay Mei and his colleagues for their endeavor and vision," said Kevin Lynch, "I am delighted to be able to work with Jay again, as well as a superb Antengene team, focused on diseases with clear unmet medical needs and a defined registration path. I am looking forward to exploring development opportunities in geographies where we have a presence, especially China, Australia and other Asian areas of R&D excellence and partnering with other pharma/biotech companies to build on each other’s strengths."

"So glad to witness the senior management team of Antengene is becoming stronger than ever," said Dr. Jay Mei, founder, chairman and CEO of Antengene. "Kevin has excellent professional skills and rich industry experience and I sincerely expect that he will make significant contributions to the clinical and corporate development of Antengene."

Kevin has published and presented widely in many leading journals and conferences, including Annals of Internal Medicine, Nature Reviews Cancer, British Journal of Cancer, Clinical Cancer Research, Journal of Clinical Oncology and Blood, and has co-authored more than 100 journal articles and conference abstracts.

Late-Breaking Clinical Trial Data for TheraSphere™ Y-90 Glass Microspheres Demonstrates Improved Survival in Primary Liver Cancer

On March 25, 2021 Boston Scientific Corporation (NYSE: BSX) reported positive data from the TARGET study of the TheraSphere Y-90 Glass Microspheres (TheraSphere) – a type of radioembolization comprised of millions of microscopic glass beads containing radioactive yttrium (Y-90) – during a late-breaking clinical trial presentation at the annual scientific meeting for the Society of Interventional Radiology (SIR) (Press release, Boston Scientific, MAR 25, 2021, View Source [SID1234577181]).

The global, retrospective TARGET study evaluated the safety and efficacy of TheraSphere therapy in patients with hepatocellular carcinoma (HCC) – the most common type of primary liver cancer – using a dosing method known as multicompartment dosimetry, which maximizes the dose of Y-90 reaching the tumor while minimizing the radiation dose that reaches normal liver tissue. In the study, imaging software was used retroactively to calculate the dose delivered within each patient’s liver tissue. Data confirmed treatment was safe and well tolerated, with only 4.8% of patients experiencing adverse events, defined in the primary endpoint as ≥ Grade 3 hyperbilirubinemia. Hyperbilirubinemia, commonly referred to as jaundice, is the build-up of bilirubin in the blood and can indicate abnormal liver function.

"The TARGET study findings create the opportunity for future TheraSphere treatment optimization and Y-90 dose escalation without compromising safety," said Prof. Marnix G.E.H. Lam, M.D., Professor of Nuclear Medicine, University Medical Center, Utrecht, Netherlands and one of the principal investigators of the TARGET study. "The study results are also generalizable and easily replicated as we included a global patient population with a wide spectrum of early, intermediate and advanced HCC."

Data from TARGET also demonstrated a correlation between the level of radiation absorbed by the tumor and an increase in survival probability through three years – with a median overall survival of 20.3 months. These findings are in line with recently published results showing that higher tumor absorbed dose leads to longer survival.i,ii In addition, a dose-efficacy relationship was established as the probability of tumor response was positively associated with the level of radiation absorbed by the tumor.

"TARGET adds to the robust body of evidence supporting TheraSphere as a safe and effective treatment option for the hundreds of thousands of patients around the world that are diagnosed with HCC each year," said Peter Pattison, president of Interventional Oncology, Peripheral Interventions, Boston Scientific. "These study insights and the Simplicit90Y software provide physicians the opportunity to develop a personalized dosing approach for their patients with the potential to improve tumor response and optimize outcomes."

TheraSphere, which was approved by the U.S. Food and Drug Administration earlier this month, is the only radioembolization technology in the U.S. indicated for the treatment of unresectable HCC.