On September 14, 2021 DNAtrix, a biotech company advancing virus-driven immunotherapies for cancer, reported the appointment of David Liebowitz, M.D., Ph.D., an industry veteran with over 20 years of experience in oncology drug and viral vaccine development, as chief medical officer (Press release, DNAtrix, SEP 14, 2021, View Source [SID1234587694]).

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"We are thrilled to welcome Dave to the executive leadership team at DNAtrix," said Jeffrey Knapp, chief executive officer of DNAtrix. "Dave has expertise in developing products that elicit immune responses against targets of interest through various therapeutic modalities, including viral-based vaccines. His deep experience leading oncology drug development programs for innovative, young, as well as established biopharmaceutical companies ­­– such as Amgen — will prove invaluable as we advance our pipeline with multiple product candidates being studied in several tumor types and two programs in pivotal stage development."

Prior to joining DNAtrix, Dr. Liebowitz was most recently vice president of Clinical Oncology at Xencor, Inc. From 2012 to 2018, he served as the chief medical officer for Vaxart, Inc., a novel vaccine development company. He was previously the Chief Scientific and Medical Officer for Vivaldi Biosciences, an influenza vaccine and therapeutics biotechnology company. Prior to that, he was the executive vice president of Research and Development at Galileo Pharmaceuticals, and he also served as co-CEO of Galileo for a period of time. Prior to joining Galileo, Dr. Liebowitz was at Amgen, where he was the director of research responsible for all oncology and vascular biology drug discovery and development programs at their Washington research site. He also managed external development collaborations and licensing activities. Dr. Liebowitz joined Amgen through their acquisition of Immunex, where he held several senior positions in clinical and preclinical development. Prior to joining Immunex, he was an associate investigator in the Abramson Cancer Institute at the University of Pennsylvania, where he was director of their immunotherapy and cellular therapy programs targeting cancer and chronic viral diseases. Dr. Liebowitz was an early recipient of a grant from the Bill and Melinda Gates foundation. He began his academic career as an assistant professor of Medicine and Virology at the University of Chicago, and was the director of the Bone Marrow Transplantation Program. Dr. Liebowitz has B.S. and M.S. degrees in Biology from Emory University, an M.D. with honors and a Ph.D. in Molecular Genetics and Cell Biology, both from the University of Chicago.

Dr. Liebowitz added, "I am impressed by the compelling clinical data for the company’s lead drug candidate, DNX-2401, in diffuse intrinsic pontine glioma (DIPG) and recurrent glioblastoma (rGBM), two tumor types that have been notoriously difficult to treat and where therapeutic advances are desperately needed. Given the promise demonstrated with these programs, I also believe there is tremendous potential to leverage DNAtrix’s oncolytic adenoviral platform further for the treatment of other tumor types, and the company has studies underway evaluating therapeutic activity in additional cancers, such as colorectal cancer."

On September 14, 2021 IO Biotech, a clinical-stage biopharmaceutical company developing novel, immune-modulating cancer therapies based on its T-win technology platform, reported that it has entered into a clinical trial collaboration and supply agreement with Merck & Co., Inc., Kenilworth, NJ, USA (known as MSD outside the US and Canada), through a subsidiary (Press release, IO Biotech, SEP 14, 2021, View Source [SID1234587693]). The purpose of the collaboration is to evaluate IO Biotech’s lead candidate, IO102-IO103, in combination with KEYTRUDA (pembrolizumab), MSD’s anti-PD-1 (programmed death receptor-1) therapy, in patients with previously untreated, unresectable or metastatic (advanced) melanoma. IO102-IO103 is an investigational cancer vaccine designed to target the immunosuppressive mechanisms mediated by key immunosuppressive proteins such as Indoleamine 2,3-dehydrogenase (IDO) and PD-L1.

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"We are pleased to collaborate with MSD to study the potential of our IDO and PD-L1 derived immune-modulating therapy in combination with KEYTRUDA as part of our broad, late-stage development program," said Mai-Britt Zocca, PhD, CEO and founder of IO Biotech. "Although therapies are available to treat metastatic melanoma, the clinical outcomes for patients with advanced disease remain poor and novel therapeutic options are desperately needed. We look forward to expanding our data set on IO102-IO103 with KEYTRUDA combination results, which we believe will support the potential approval of IO102-IO103 as a first-line therapy for melanoma and other difficult-treat-cancers."

The planned Phase 3 trial will be an open label, randomized clinical trial that will evaluate the combination of IO102-IO103 with MSD’s anti-PD-1 therapy, KEYTRUDA, versus KEYTRUDA alone in patients with previously untreated, unresectable or metastatic (advanced) melanoma. Biomarker studies will also be conducted. Under the terms of the agreement, IO Biotech will sponsor the Phase 3 trial and MSD will supply KEYTRUDA.

In a Phase 1/2 clinical trial of 30 patients with metastatic melanoma, IO102-IO103, in combination with anti PD1 mAb, demonstrated an ability to induce meaningful tumor regression and establish durable antitumor response while achieving a manageable tolerability profile for patients. In this trial, we observed a confirmed overall response rate (ORR) of 73% and a complete response (CR) rate of 47%. Based on the results from this trial, IO102-IO103, in combination with pembrolizumab, was granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA) for treatment of unresectable/metastatic melanoma.

About IO102-IO103/KEYNOTE-D18:

An open label, randomized Phase 3 clinical trial of IO102-IO103 in combination with pembrolizumab versus pembrolizumab alone in patients with previously untreated, unresectable or metastatic (advanced) melanoma

Biomarker studies will be conducted in parallel to the above.

The clinical trials will be sponsored by IO Biotech. IO Biotech maintains global commercial rights to IO102-IO103.

On September 14, 2021 Convergent Therapeutics Inc., a clinical stage radiopharmaceutical company, and POINT Biopharma Global Inc., (Nasdaq: PNT) ("POINT") a company accelerating the discovery, development and global access to life changing radiopharmaceuticals, reported a collaboration to evaluate the combination of CONV 01-α (225Ac−J591, or rosopatamab-225Ac), Convergent’s antibody directed at prostate-specific membrane antigen (PSMA) coupled with Actinium-225 (225Ac), an alpha particle emitter and POINT’s PSMA radioligand PNT2002 linked to Lutetium-177 (177Lu), a beta particle emitter in men with progressive metastatic castration-resistant prostate cancer (mCRPC) in a Phase I/II investigator-initiated trial (Press release, Convergent Therapeutics, SEP 14, 2021, View Source;rosopatamab-225ac-in-combination-with-pnt2002-for-progressive-metastatic-castration-resistant-prostate-cancer-301375737.html [SID1234587692]). The study has begun patient accrual and is being conducted at Weill Cornell Medicine with Dr. Scott T. Tagawa, Professor of Medicine and Professor of Medicine in Urology at Weill Cornell Medicine, as Principal Investigator.

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The Phase I/II trial is enrolling up to 33 patients with progressive mCRPC who have received a prior androgen receptor signaling inhibitor (ARSI) and taxane chemotherapy and are PSMA PET-positive. The open-label Phase I dose-escalation portion of the study is designed to determine the maximum tolerated dose (MTD) for the combination of CONV 01-α and PNT2002. PNT2002 will be administered at the dose utilized in POINT Biopharma’s Phase III SPLASH trial. Escalating doses of CONV 01-α will be administered concurrently, starting with doses previously demonstrated to be well-tolerated. After the Phase I study has established the MTD of the CONV 01-α and PNT2002 combination, investigators will initiate the Phase II expansion study study at MTD. The primary objective of the Phase II study is to assess the number of patients who demonstrate a >50% prostate-specific antigen (PSA) decline following treatment.

The co-targeting treatment approach is based on the research of Dr. Neil Bander, the Bernard & Josephine Chaus Professor of Urologic Oncology at Weill Cornell Medicine, who discovered the synergy between radioligands and 225Ac−J591. The finding that antibodies synergistically improve the efficacy of ligand-targeted agents is the subject of patent filings by Cornell University that, in turn, have been exclusively licensed to Convergent Therapeutics, inc. At the ASCO (Free ASCO Whitepaper) 2021 Annual Meeting in June, Dr. Tagawa presented proof of concept data that demonstrated that a single dose of CONV 01-α had anti-tumor activity in heavily pretreated men with mCRPC.

Dr. Philip Kantoff, Chief Executive Officer of Convergent Therapeutics, stated, "Within the field, there is significant and growing interest in our differentiated approach that leverages the complementary advantages of co-targeting surface cancer molecules such as PSMA with both antibodies and small molecule ligands, as well as alpha and beta radiopharmaceuticals. This collaboration with POINT Biopharma will, therefore, help to facilitate and validate our disruptive strategy of combining radioligands and antibodies carrying different payloads, directed at a cancer target, in order to significantly improve the efficacy of radiopharmaceutical therapies. Our long-term goal is to meaningfully improve outcomes in patients with prostate cancer and to leverage this combinatorial platform to treat other cancers. We look forward to evaluating the results once they are available."

Dr. Joe McCann, Chief Executive Officer of POINT Biopharma, noted, "Combination therapies are a very exciting opportunity in the radiopharmaceutical space, as demonstrated by Dr. Bander’s research into combining different radioligand therapies to improve outcomes. To date, PNT2002 has shown promise as a monotherapy and we believe that this collaboration has the potential to not only improve patient outcomes, but also provide patients and physicians with new therapeutic options for advanced prostate cancers."

For additional information about this clinical trial, please visit www.clinicaltrials.gov, NCT04886986

Dr. Bander is a co-founder with equity and a paid scientific advisor for Convergent Therapeutics, Inc. Dr. Tagawa is a paid consultant and receives equity for Convergent Therapeutics, Inc.

About PNT2002
PNT2002 is a PSMA-targeted radioligand in development for the treatment of patients with metastatic castration-resistant prostate cancer who have progressed following treatment with ARSI therapy. The Phase 3 SPLASH study (NCT04647526) is a multi-center, randomized, open label assessment of PNT2002 in patients with PSMA-expressing mCRPC who have progressed on ARSI therapy and refuse or not eligible for chemotherapy. The next phase of the study is expected to enroll approximately 400 patients across North America, Europe and the UK, and top-line data from the SPLASH study is expected to report in mid-2023.

On September 14, 2021 Specialised Therapeutics reported that AUSTRALIAN patients with an aggressive form of lung cancer (metastatic Small Cell Lung Cancer) can now access a new therapy that may improve outcomes (Press release, Specialised Therapeutics Asia, SEP 14, 2021, View Source [SID1234587691]).

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The therapy, ZEPZELCA (lurbinectedin) has been approved by the Therapeutic Goods Administration (TGA) "for the treatment of patients with metastatic small cell lung cancer (SCLC) that has progressed on or after prior platinum-containing therapy".1

This means patients who have failed other existing treatment options will now be able to access another line of therapy.

ZEPZELCA is the first new therapy approved by the TGA to treat second-line SCLC in more than two decades.

Australian lung cancer oncologist Professor Paul Mitchell from the Olivia Newton-John Cancer and Wellness and Research Centre said SCLC was particularly aggressive and more than two-thirds of patients were diagnosed with extensive stage disease. He said fewer than 5% of these patients currently survived more than five years post diagnosis. 3,4

"The new availability of ZEPZELCA will be welcomed by patients, families and the medical community, as we strive to improve patient outcomes for this disease," Professor Mitchell said.

"With this approval, we now have another option for patients who have progressed after prior platinum-based treatments. This provides an opportunity for them to continue treatment and potentially, improve outcomes."

The TGA approval of ZEPZELCA has been granted under a provisional regulatory pathway. The US Food and Drug Administration (FDA) and Australia’s Therapeutic Goods Administration (TGA) collaborated via ‘Project Orbis’ to accelerate availability to Australian patients.

ZEPZELCA’s approval is based on clinical data from an open-label, multi-centre, single-arm phase II study in 105 adult patients with SCLC who had disease progression after treatment with platinum-based chemotherapy.2

The data, which appeared in The Lancet Oncology May 2020 issue, demonstrated that in patients with relapsed SCLC, ZEPZELCA provided an Overall Response Rate (ORR) of 35% and a median duration of response of 5.3 months as measured by investigator assessment (30% and 5.1 months respectively, as measured by an independent review committee (IRC).2

The provisional approval is the subject of a further confirmatory study in more than 700 patients with 2nd line SCLC including some Australian sites. This study is expected to be completed in 2025.

ZEPZELCA is being made available in Australia by the independent pharmaceutical Company, Specialised Therapeutics (ST), under exclusive license from international partner, PharmaMar.

ST Chief Executive Officer Mr Carlo Montagner said the approval of ZEPZELCA would potentially make a difference for around 400 Australian patients annually who had run out of treatment options.

"We are delighted to be able to provide a new therapy option for patients with this difficult to treat cancer," he said.

"While patients may initially respond to traditional chemotherapy, they often experience an aggressive recurrence that is historically resistant to treatment.

"Our mission has always been to provide therapies in areas of unmet need and SCLC is certainly one of these areas. We look forward to making a difference for these patients and their families."

PharmaMar president José María Fernández Sousa-Faro, PhD, said the Company was delighted Australian patients would now be provided access to ZEPZELCA.

"We are pleased to bring a new treatment choice to relapsed SCLC patients. "The accelerated approval of ZEPZELCA underscores its potential to fill an unmet need in this often-overlooked SCLC community."

ZEPZELCA is currently available in Australia via a Special Access Program.

Commercial supplies of ZEPZELCA will commence early 2022.

About Small Cell Lung Cancer (SCLC)

SCLC is a particularly aggressive type of lung cancer that represents approximately 10-15% of all lung cancers,3 accounting for more than 275,000 new cases worldwide every year. In Australia, around 1,900 patients are diagnosed annually with the disease,4 which is characterised by rapid growth, early dissemination that is often asymptomatic and with acquired resistance to drugs2. SCLC is staged into limited-stage or extensive-stage disease. Limited-stage disease is potentially curable with aggressive therapy consisting of concurrent chemoradiotherapy, prophylactic cranial irradiation, and occasionally, surgery. However, nearly two-thirds of SCLC patients have extensive-stage disease at diagnosis, which is not curable, and patients are currently treated with palliative intent, with a median survival of 7 to 11 months after diagnosis and with less than 5% survival at 2 years.5,6

About ZEPZELCA (lurbinectedin)

ZEPZELCA also known as PM1183, is an alkylating drug that binds guanine residues within DNA. This triggers a cascade of events that can affect the activity of DNA binding proteins, including some transcription factors, and DNA repair pathways, resulting in disruption of the cell cycle and eventual cell death.1

ZEPZELCA 4 mg is a prescription medicine used to treat adults with a kind of lung cancer called small cell lung cancer (SCLC) that has spread to other parts of the body (metastatic) and who have received treatment with chemotherapy that contains platinum, and it did not work or is no longer working. ZEPZELCA is approved based on response rate and how long the response lasted. Additional studies will further evaluate the benefit of ZEPZELCA for this use.

About the Phase II Monotherapy Trial
The Phase II trial of ZEPZELCA was an open-label, single-arm study, which enrolled a total of 105 SCLC patients at 26 hospitals in six European countries and the U.S.2 In the trial, platinum-sensitive and platinum-resistant patients were treated with ZEPZELCA 3.2 mg/m2, administered as a 60-minute IV infusion repeated every 21 days until disease progression or unacceptable toxicity. The primary endpoint, ORR, was 35% and the median duration of response was 5.3 months as measured by investigator assessment (30% and 5.1 months respectively, as measured by an IRC).2 Serious adverse reactions in ≥3% of patients included pneumonia, febrile neutropenia, neutropenia, respiratory tract infection, anaemia, dyspnoea, and thrombocytopenia. ZEPZELCA was discontinued in 1.9% of patients and was delayed in 30.5% of patients due to an adverse reaction. Dose reductions for an adverse reaction occurred in 25 percent of patients.2

On September 14, 2021 Harbour BioMed ("HBM", HKEX: 02142) reported that the China National Medical Products Administration (NMPA) has approved its Investigational New Drug (IND) applications for HBM4003, a next-generation, fully human anti-CTLA-4 monoclonal heavy chain only antibody in combination with PD-1 antibody in patients with advanced hepatocellular carcinoma (HCC) and other solid tumors, as well as advanced neuroendocrine tumor/neuroendocrine carcinoma (NET/NEC) and other solid tumors (Press release, Harbour BioMed, SEP 14, 2021, View Source [SID1234587690]).

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HBM4003 has already received an IND approval from the U.S. FDA, IND approvals from the China NMPA and the clinical trial approval from the Australia Institutional Review Board (IRB). The Company is proceeding multiple clinical trials for HBM4003 monotherapy and combination therapy across the world.

"HBM4003 has already demonstrated encouraging safety and anti-tumor activity in patients in our ongoing trials. The NMPA’s two IND approvals are the continuing recognition of this next-generation anti-CTLA-4 antibody, reminding us of our responsibility and mission. We look forward to bringing this novel combination therapeutic to HCC and NET/NEC patients soon," said Dr. Jingsong Wang, Founder, Chairman and CEO of Harbour BioMed.

About HBM4003

HBM4003 is a fully human anti-CTLA-4 monoclonal heavy chain only antibody (HCAb) generated from Harbour Mice. By enhancing antibody-dependent cell cytotoxicity (ADCC) killing activity, HBM4003 has demonstrated significantly improved depletion specific to high CTLA-4 Treg cells in tumor tissues. The potent anti-tumor efficacy and differentiated pharmacokinetics with durable pharmacodynamic effect presents a favorable product profile. This novel and differentiated mechanism of action has the potential to improve efficacy while significantly reducing the toxicity of the drug in monotherapy and combo-therapy.

About Hepatocellular Carcinoma (HCC)

Liver cancers are the fourth most common cause of cancer-related death and rank sixth in terms of incident cases worldwide. On the basis of annual projections, the World Health Organization estimates that more than 1 million patients will die from liver cancer in 2030.1 Hepatocellular carcinoma (HCC)2 is the most common form of liver cancer and accounts for ~90% of cases. The majority of HCC occur in patients with underlying liver diseases, mostly as results of hepatitis B or C virus (HBV or HCV) infection or alcohol abuse. Systemic therapies are recommended for advanced stage of HCC, including inhibitors of multiple kinases and immune-based therapies, with increased median survival of 10.6~15.6 months.1 Although the clinical management of advanced stage of HCC has improved in the past 10 years, there is still high unmet medical needs to explore new, effective and life-prolonged therapies for HCC.

About Neuroendocrine Neoplasms (NEN, including NET and NEC)

NEN is a neoplasm that arise from neuroendocrine cells. There are two fundamentally different groups of NEN: well-differentiated, low-proliferating NEN, called neuroendocrine tumor (NET) and poorly differentiated, highly proliferating NEN, called neuroendocrine carcinoma (NEC). NEN can occur almost everywhere in the body but are most common in the gastrointestinal tract, the pancreas, and the lungs.3 Surgery, radiation therapy, chemotherapy and a variety of drug treatments are common therapies for patients with NET/NEC. Prognosis is worse in metastatic tumors, with the 5-year survival rate about 4.7% in metastatic gastroenteropancreatic neuroendocrine cancer (GEP-NEC).4 Consequently, there is still high unmet medical needs to explore new, effective and convenient therapies for NET/NEC.