On September 14, 2021 LeaderMed Health Group Limited, a pharmaceutical development company with operations based in Asia, and OPKO Health, Inc. (NASDAQ: OPK), a diversified healthcare company focused on diagnostics and pharmaceuticals, reported the formation of a joint venture to develop, manufacture and commercialize two of OPKO’s clinical stage, long-acting drug products in Greater China and eight other Asian territories (Press release, Opko Health, SEP 14, 2021, View Source [SID1234587674]).

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Under the terms of the agreements, OPKO will grant the joint venture exclusive rights to develop, manufacture and commercialize (a) OPK88003, an oxyntomodulin analog being developed for the treatment of obesity and diabetes, and (b) Factor VIIa-CTP, a novel long-acting coagulation factor being developed to treat hemophilia, in exchange for a 47% ownership interest in the joint venture. In addition, OPKO will receive an upfront payment of $1 million and will be reimbursed for clinical trial material and technical support it provides the joint venture.

LeaderMed will be responsible for funding the joint venture’s operations, development and commercialization efforts and will, with its syndicate partners, initially invest $11 million in exchange for a 53% ownership interest. OPKO retains full rights to oxyntomodulin and Factor VIIa-CTP in all other geographies.

"Through this joint venture, we have an opportunity to extend the global availability of two of our novel long-acting development products and to establish a presence in China in partnership with collaborators who have significant experience and deep knowledge of the Asian biopharmaceutical opportunity," said Phillip Frost, M.D., Chairman and Chief Executive Officer of OPKO.

"LeaderMed Group is an innovative pharmaceutical development company with its own pipeline of licensed products. Our capabilities include an experienced management team with demonstrated success in bringing biopharmaceutical and pharmaceutical products to market in China and globally, cGMP facilities to manufacture clinical-grade products, and a corporate charter that acknowledges and protects client IP. We are excited about the opportunity to expeditiously deliver a novel and superior treatment for obesity and diabetes to hundreds of millions of patients in China and Asia, as well as a treatment for hemophilia, an orphan indication," added Dr. Joanne Jiang, Chief Executive Officer of LeaderMed Group and architect of the joint venture.

About Oxyntomodulin
Oxyntomodulin is a naturally occurring hormone produced in the colon that binds the GLP-1 and glucagon receptors, regulating both blood glucose appetite and lipid metabolism. OPKO Health is developing OPK88003, a long-acting, once-weekly oxyntomodulin analog for the treatment of type 2 diabetes and obesity. OPK88003 has been successfully studied in two Phase 2 clinical trials enrolling type 2 diabetes patients, studying weight loss and reduction in glycosylated hemoglobin (HbA1c or A1c), a marker of sugar metabolism. Driven by the LeaderMed-OPKO joint venture, it is positioned to be the first dual-targeted drug approved for diabetes and obesity in the Chinese and Asia markets.

About Factor VIIa-CTP
Factor VIIa-CTP is a novel, long-acting recombinant Factor VIIa utilizing OPKO’s proprietary technology to extend its circulatory half-life without the use of polymers, encapsulation techniques or nanoparticles. The technology is based on a naturally occurring peptide, the C-terminal peptide (CTP) of the beta chain of human chorionic gonadotropin. The CTP technology is also used in OPKO’s hGH-CTP (somatrogon), a long-acting recombinant human growth hormone product that successfully completed Phase 3 clinical trials in children with growth hormone deficiency. hGH-CTP has been submitted for approval in the United States, Europe and Japan and is partnered with Pfizer for global commercialization. Factor VIIa-CTP has been granted orphan drug designation in the U.S. and Europe.

In China, hemophilia was designated as a rare disease in 2018. LeaderMed expects to seek fast regulatory approval for Factor VIIa-CTP through a special national rare disease channel.

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.

On September 14, 2021 Sanofi reported the completion of its acquisition of Translate Bio, further accelerating the company’s efforts to develop transformative vaccines and therapies using mRNA technology (Press release, Sanofi, SEP 14, 2021, View Source [SID1234587675]). The acquisition adds a critical pillar to the company’s mRNA Center of Excellence which aims to unlock the potential of next-generation mRNA vaccines and other strategic areas such as immunology, oncology, and rare diseases.

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The tender offer for all of the outstanding shares of Translate Bio common stock expired as scheduled at one minute after 11:59 p.m., Eastern Time, on Monday, September 13, 2021. The minimum tender condition and all of the other conditions to the offer have been satisfied and on September 14, 2021, Sanofi accepted for payment and will promptly pay for all shares validly tendered and not validly withdrawn.

Following its acceptance of the tendered shares, Sanofi completed its acquisition of Translate Bio through the merger of a wholly owned subsidiary of Sanofi with and into Translate Bio, pursuant to Section 251(h) of the General Corporation Law of the State of Delaware, with Translate Bio continuing as the surviving corporation and becoming an indirect, wholly owned subsidiary of Sanofi.

In connection with the merger, all Translate Bio shares not validly tendered in the tender offer have been converted into the right to receive the same $38 per share in cash, without interest thereon and net of any applicable withholding taxes, that would have been paid had such shares been validly tendered in the tender offer. As of September 14, 2021, Translate Bio common stock will cease to be traded on the NASDAQ Global Select Stock Market.

Morgan Stanley & Co. International plc acted as exclusive financial advisor to Sanofi while Weil, Gotshal & Manges LLP acted as legal counsel. Centerview Partners acted as lead financial advisor to Translate Bio in the transaction, while Paul, Weiss, Rifkind, Wharton & Garrison LLP acted as legal counsel. Evercore also acted as a financial advisor in this transaction to Translate Bio. MTS Health Partners, LP also gave financial advice to Translate Bio.

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 Pacylex Pharmaceuticals, Inc. reported that it initiated a Phase 1 clinical trial of PCLX-001, a first-in-class, orally bioavailable small molecule inhibitor of N-myristoyltransferase 1 and 2 (NMT1, NMT2), at the University of Alberta Cross Cancer Institute (Press release, Pacylex Pharmaceuticals, SEP 14, 2021, View Source [SID1234645062]). This open label, dose escalation study will examine the safety and tolerability of PCLX-001 and determine the dose to be used in initial efficacy studies. Pacylex received a No Objection Letter from Health Canada on March 8, 2021, authorizing the planned Phase 1 Trial of PCLX-001 in relapsed/refractory B-cell Non-Hodgkin’s Lymphoma and advanced solid malignancies. PCLX-001 is believed to be the first NMT inhibitor that will be clinically tested.

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PCLX-001 is the first clinical candidate sponsored by Pacylex Pharmaceuticals to reach the clinical stage. "We are excited to see PCLX-001 transition to helping serious refractory cancer patients," said Michael Weickert, CEO of Pacylex Pharmaceuticals. "Our mission is to bring this new potential cancer breakthrough to patients, and we are especially privileged to be working with the Cross Cancer Institute on this clinical program."

"We are genuinely excited to initiate a new therapeutic candidate for these very challenging patients," said Dr. John Mackey, the Chief Medical Officer of Pacylex Pharmaceuticals. "Based on its unique mechanism of action and preclinical results, we hope this therapy will provide at least some patients with relief from their disease."

Dr. Randeep Sangha is the principal investigator for the study of PCLX-001 at the Cross Cancer Institute in Edmonton. "We plan to test PCLX-001 on patients who have tried everything else. Testing something really new is the goal of every cancer researcher since it may open the door for new treatments for patients" said Dr. Sangha.

Patient enrollment and dosing will also begin soon at Princess Margaret Hospital in Toronto and the BC Cancer Agency in Vancouver. The study will enroll 20-30 patients in the initial phase. Three principal investigators will oversee the clinical study at the three clinical sites in Canada: Dr. John Kuruvilla at Princess Margaret Cancer Centre in Toronto, Dr. Randeep Sangha at the Cross Cancer Institute in Edmonton, and Dr. Laurie Sehn at the British Columbia Cancer Center in Vancouver.

This study is registered at ClinicalTrials.gov Identifier: NCT04836195.

About Non-Hodgkin’s Lymphoma

Non-Hodgkin’s Lymphoma (NHL) is the most common hematologic malignancy and the eleventh most common cancer worldwide, with nearly 510,000 new cases diagnosed in 2018. It accounted for nearly 249,000 deaths worldwide in 2018. The most prevalent form of NHL, accounting for about 40% of newly diagnosed NHL cases, is an aggressive form called diffuse large B-cell lymphoma (DLBCL), that comes with a life expectancy of weeks or months if left untreated.

PCLX-001

PCLX-001 is a small molecule, first-in-class N-myristoyltransferase (NMT) inhibitor, originally developed by the University of Dundee Drug Discovery Unit as part of a program to treat African sleeping sickness funded by Wellcome Trust. Pacylex is developing PCLX-001, which has excellent oral bioavailability, to treat leukemia and lymphoma. PCLX-001 selectively kills cancer cells and completely regresses (eliminates) tumors in animal models of acute myeloid leukemia (AML), diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL). PCLX-001 has also been shown to strongly inhibit the growth of lung and breast cancer tumors in animal models. In leukemia, lymphoma and breast cancer patients, the level of NMT2 is correlated with survival, suggesting an important biological role in these cancers. In tests using cultured cancer cells in vitro, PCLX-001 is at least ten times as potent as ibrutinib (Imbruvica) and dasatinib (Sprycel), two clinically approved drugs currently used to treat hematologic malignancies.