On June 28, 2018 BioAtla, LLC, a global biotechnology company focused on the development of Conditionally Active Biologic (CAB) protein therapeutics, reported the treatment of the first patient in its clinical trial BA3021-001 for BioAtla’s BA3021, a novel conditionally active ROR2-targeted antibody-drug conjugate (CAB-ROR2-ADC) (Press release, BioAtla, JUN 28, 2018, View Source [SID1234527502]). This is a multi-center, open-label, Phase 1/2 study designed to evaluate the safety, tolerability, pharmacokinetics, immunogenicity and antitumor activity of BA3021 in patients with advanced solid tumors including non-small cell lung cancer (NSCLC), triple negative breast cancer and soft tissue sarcoma. CAB-ROR2-ADC is BioAtla’s second CAB investigational product to enter clinical trials following BA3011, CAB-AXL-ADC in February of this year.

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The first patient in the BA3021 clinical study was enrolled and dosed at Sarah Cannon Research Institute at Tennessee Oncology in Nashville, TN under the direction of the principal investigator, Howard A. "Skip" Burris III, MD. Dr. Burris, a recognized leader in clinical oncology, serves as chief medical officer and president of clinical operations at Sarah Cannon. "Innovative advancements in the treatment of cancer include tumor specific activation of therapy and promoting appropriate immune response. Providing access to cutting-edge therapies in clinical trials, such as the BA3021 clinical study, further supports our mission to advance care for cancer patients," said Dr. Burris.

The ROR2 transmembrane protein tyrosine kinase is an onco-fetal protein that acts as a non-canonical Wnt 5A receptor. ROR2 is found to be highly expressed during embryonic development and in several important cancer types, and the level of expression in tumors is tightly correlated with patient prognosis. Recently, ROR2 and its ligand Wnt 5A have been shown to be induced in cancers that are resistant to treatment with immune checkpoint inhibitors such as anti-PD-1 antibody immune therapy suggesting a mechanistic role of this receptor-ligand axis in resistance to standard cancer treatments resulting in relapsing, minimal residual disease. However, low to moderate levels of expression of ROR2 in multiple normal adult tissues are predicted based on RNA expression, histological analysis and functional studies. To minimize the risk of potential disruption of normal function of ROR2 receptors on normal cells, BioAtla applies its proprietary CAB technology to develop its CAB antibody-drug conjugate (ADC) targeting ROR2 with the intent to activate binding to the ROR2 receptor only in the tumor microenvironment and deliver the toxic payload to the cancerous cells. The CAB-ROR2-ADC BA3021 is designed to maximize efficacy on ROR2 expressing tumors while minimizing toxicity, leading to better clinical outcomes.

About Conditionally Active Biologics (CABs)

Conditionally Active Biologic proteins are generated using BioAtla’s proprietary protein discovery, evolution and expression technologies. These proteins can be monoclonal antibodies, enzymes and other proteins designed with functions dependent on changes in microphysiological conditions (e.g., pH level, oxidation, temperature, pressure, presence of certain ions, hydrophobicity and combinations thereof) both outside and inside cells.

Studies have shown that cancerous tumors create highly specific conditions at their site that are not present in normal tissue. These cancerous microenvironments are primarily a result of the well understood unique glycolytic metabolism associated with cancer cells, referred to as the Warburg Effect. CAB proteins are designed to deliver their therapeutic payload and/or recruit the immune response in specific and selected locations and conditions within the body and to be active only in the presence of a particular cellular microenvironment. In addition, the activation is designed to be reversible to repeatedly switch ‘on and off’ should the CAB move from a diseased to a normal cellular microenvironment and vice versa. CABs can be developed in a variety of formats including antibodies, antibody drug conjugates (ADCs), bi-specifics, chimeric antigen receptor T-cells (CAR-Ts) and combination therapies.

On June 28, 2018 MolMed S.p.A. (MLMD.MI), a medical biotechnology company focusing on research, development, manufacturing, and clinical validation of cell & gene therapies to treat cancer and rare diseases and AbCheck s.r.o., a technology company focusing on the discovery and optimization of high-quality human antibodies, reported that they have entered into a three-year Master Agreement aimed at providing MolMed with selected and optimized antibodies for the development of new Chimeric Antigen Receptors (CARs), targeting both liquid and solid tumors (Press release, MolMed, JUN 28, 2018, View Source [SID1234527504]).

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Under the agreement, AbCheck will use its proprietary discovery platform to select, optimize and deliver multiple human single-chain variable fragments (scFvs), specifically recognizing each MolMed target candidate. ScFvs are the extracellular regions of the CAR responsible for antigen recognition and binding, conferring specificity to the CAR.

The new and optimized scFvs delivered by AbCheck will allow MolMed to expand its proprietary pipeline in both autologous CAR-T and future allogenic CAR-NK platforms.

Riccardo Palmisano, MolMed CEO, commented: "This new collaboration plays a key role to complete the picture of the planned and announced enlargement of our CAR pipeline. Leveraging on the unique experience that we developed on CAR T CD44v6, now close to clinical stage in acute myeloid leukemia and multiple myeloma and on the recently signed partnership with Glycostem, with this agreement with AbCheck, a company with extensive expertise in antibodies selection and boasting partnerships with relevant companies and institutions in the CAR field, MolMed is fully prepared to build a robust autologous and allogeneic original CAR T pipeline, able to target both liquid and solid tumors".

Volker Lang, Managing Director of AbCheck, added: "AbCheck is recognized for its proven capability to reliably deliver high-quality human antibodies suitable for clinical development. We are very pleased to employ our unique technology suite to support MolMed’s dedicated team in adding novel therapeutic options to its diverse pipeline. Both CAR-Ts and CAR-NKs represent promising novel immuno-oncology approaches and we are confident that AbCheck’s abilities in antibody discovery and optimization will be an important asset in developing such approaches."

On June 27, 2018 Purdue Pharma L.P. reported successful completion of a first-in-human Phase 1 dose escalation study of tinostamustine in patients with relapsed or refractory hematological malignancies for which there are no available therapies (Press release, Purdue Pharma, JUN 27, 2018, View Source [SID1234527497]). The study evaluated the safety and pharmacokinetics, and sought to determine the maximum tolerated dose and inform a Phase 2 dose of tinostamustine. 1

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The multi-acting therapy candidate tinostamustine, previously known as EDO-S101, is a novel and potentially first-in-class alkylating deacetylase inhibitor (AK-DACi) therapy being studied for its potential to improve access to the DNA strands within cancer cells, break them, and counteract the cancer cells’ attempt to repair the DNA damage. It is in development for a range of rare or difficult to treat blood cancers and solid tumors. Based on the results of this Phase I human trial, Purdue will support advancement of tinostamustine into further clinical studies.

"We are pleased with the outcome of this promising early stage oncology program and we believe it has the potential to make meaningful clinical contributions in areas with significant unmet needs," said Craig Landau, MD, president and CEO, Purdue Pharma. "In addition to our established commitments in oncology and neuroscience, we are actively seeking opportunities to collaborate across a number of therapeutic areas as part of our ongoing efforts to diversify our scientific research and bring therapies to market that may improve outcomes for patients."

The reported completion of this study is the first clinical update since Purdue announced in November 2017 significant oncology-related investments to establish a portfolio of drug candidates with the potential to deliver new cancer therapies, in areas of high unmet medical need, to physicians and patients. As part of these investments, Purdue is currently supporting research for four drug candidates across 14 different cancer types. Research on these compounds is being advanced on behalf of Purdue by Mundipharma EDO.

In addition to tinostamustine, Purdue’s clinical stage oncology portfolio includes etoposide toniribate, a novel target-activated topoisomerase inhibitor that delivers the chemotherapy etoposide to tumors in an inactive form where it is ‘switched on’ by enzymes called carboxylesterases. Purdue also has two late pre-clinical stage antibody-drug conjugates, EDO-B776 and EDO-B278, in development. EDO-B776 is being studied for its potential to target the cancer antigen 125 (CA-125) in ovarian cancer. EDO-B278, which targets human tissue factor, is in development for treatment of various solid tumors.

The decision to move tinostamustine into Phase 1 human trials was supported by preclinical studies, which suggest that tinostamustine may deliver both alkylating activity and pan-histone deacetylase (HDAC) inhibition to improve access to the DNA strands within cancer cells, break them, and counteract the cancer cells’ attempt to repair the DNA damage.

Purdue will also continue to selectively seek additional oncology product assets through licensing and acquisition, and the company will maintain a priority interest in candidates with mechanisms complementary to emerging immuno-oncology based treatment paradigms

On June 27, 2018 Forty Seven, Inc. (Nasdaq:FTSV), a clinical stage immuno-oncology company, reported the pricing of its initial public offering of 7,035,000 shares of common stock at a price to the public of $16.00 per share (Press release, Forty Seven, JUN 27, 2018, View Source [SID1234527522]). In addition, Forty Seven has granted the underwriters a 30-day option to purchase up to an additional 1,055,250 shares of common stock solely to cover over-allotments, if any, at the initial public offering price less underwriting discounts and commissions. The shares are expected to begin trading on The Nasdaq Global Select Market under the symbol "FTSV" on June 28, 2018.

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Morgan Stanley and Credit Suisse are acting as lead bookrunners, Canaccord Genuity is acting as lead manager, and BTIG and Oppenheimer & Co. Inc. are acting as co-managers for the offering.

The offering is being made only by means of a prospectus. A copy of the final prospectus, when available, may be obtained from Morgan Stanley & Co. LLC, Attention: Prospectus Department, 180 Varick Street, Second Floor, New York, New York 10014; or Credit Suisse Securities (USA) LLC, Attention: Prospectus Department, One Madison Avenue, New York, New York, 10010 or by email at [email protected].

A registration statement relating to these securities has been filed with, and declared effective by, the Securities and Exchange Commission. This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation, or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On June 27, 2018 AstraZeneca and Merck & Co., Inc., Kenilworth, N.J., US (Merck: known as MSD outside the US and Canada) reported positive results from the randomised, double-blinded, placebo-controlled, Phase III SOLO-1 trial of Lynparza (olaparib) tablets (Press release, AstraZeneca, JUN 26, 2018, View Source [SID1234527478]).

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Women with BRCA-mutated (BRCAm) advanced ovarian cancer treated 1st-line with Lynparza maintenance therapy had a statistically-significant and clinically-meaningful improvement in progression-free survival compared to placebo. The safety and tolerability profile of Lynparza was consistent with previous trials. Based upon these data, AstraZeneca and MSD plan to initiate discussions with health authorities regarding regulatory submissions.

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "For the first time, we see a significant and clinically-impactful improvement in progression-free survival in the 1st-line maintenance setting for women with BRCA-mutated ovarian cancer treated with a PARP inhibitor. The SOLO-1 data reinforce the importance of knowing BRCA status at diagnosis, as this may enable women with BRCA-mutated ovarian cancer to receive Lynparza earlier. We would like to thank the investigators, hospitals and most of all the patients who took part in this trial, without whom medical advancements would not be possible."

Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, MSD Research Laboratories, said: "Building on the strong data we’ve seen with Lynparza to date, the data from SOLO-1 reinforces Lynparza’s ability to provide meaningful disease control with a well-characterised safety and tolerability profile. We look forward to presenting the full data set for SOLO-1 at a future medical meeting and working with regulatory authorities to bring Lynparza to women with ovarian cancer in the 1st-line maintenance setting as quickly as possible."

Additionally, the ongoing GINECO/ENGOTov25 Phase III trial, PAOLA-1, is testing the effect of Lynparza in combination with bevacizumab as a 1st-line maintenance treatment in women with newly-diagnosed advanced ovarian cancer, regardless of their BRCA status. Results are expected in 2019.

NOTES TO EDITORS
About SOLO-1

SOLO-1 is a Phase III randomised, double-blinded, placebo-controlled, multicentre trial to evaluate the efficacy and safety of Lynparza tablets as 1st-line maintenance monotherapy compared with placebo, in patients with BRCAm advanced ovarian cancer. The trial randomised 391 patients with a deleterious or suspected deleterious BRCA1 or BRCA2 mutation who were in clinical complete or partial response following platinum-based chemotherapy. Eligible patients were randomised (2:1) to receive Lynparza 300mg tablets twice daily or placebo tablets twice daily. The primary endpoint was progression-free survival and key secondary endpoints included time to second disease progression or death and overall survival.

About ovarian cancer

Worldwide, ovarian cancer is the seventh most common cancer and the eighth leading cause of cancer death in women. The five-year survival rate for ovarian cancer worldwide is 30-40%. In 2012, there were nearly 239,000 new cases diagnosed and around 152,000 deaths. For newly diagnosed advanced ovarian cancer, the primary aim of treatment is to delay progression of the disease for as long as possible and maintain the patient’s quality of life with the intent of achieving complete remission or cure.

About BRCA mutations

BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA and play an important role in maintaining the genetic stability of cells. When either of these genes is mutated, or altered, such that its protein product either is not made or does not function correctly, DNA damage may not be repaired properly and cells become unstable. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer.

About Lynparza
Lynparza (olaparib) was the first-in-class PARP inhibitor and the first targeted treatment to potentially exploit DNA damage response (DDR) pathway deficiencies, such as BRCA mutations, to preferentially kill cancer cells. Specifically, in vitro studies have shown that Lynparza-induced cytotoxicity may involve inhibition of PARP-enzymatic activity and increased formation of PARP-DNA complexes, resulting in DNA damage and cancer cell death. Lynparza is being tested in a range of DDR-deficient tumour types.

Lynparza, which is being jointly developed and commercialised by AstraZeneca and MSD, is approved for advanced ovarian cancer and metastatic breast cancer and has been used in over 20,000 patients worldwide. Lynparza has the broadest and most advanced clinical trial development programme of any PARP inhibitor and AstraZeneca and MSD are working together to deliver it as quickly as possible to more patients across multiple cancer types. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.