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Scholar Rock to Develop Cancer Immunotherapy Product Candidate, SRK-181, a Selective Inhibitor of TGFβ1 Activation, to Overcome Checkpoint Inhibitor Resistance

On March 12, 2019 Scholar Rock Holding Corporation (NASDAQ:SRRK), a clinical-stage biopharmaceutical company focused on the treatment of serious diseases in which protein growth factors play a fundamental role, reported that it has selected SRK‑181, a highly specific inhibitor of TGFβ1 activation, as the first product candidate in its TGFβ1 cancer immunotherapy program based on the strength of its preclinical data and human translational insights (Press release, Scholar Rock, MAR 12, 2019, View Source [SID1234537354]). Scholar Rock has initiated manufacturing and is progressing preclinical development efforts with plans to initiate a Phase 1 trial in patients with solid tumors in mid- 2020.

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"Given that a majority of cancer patients fail to respond to checkpoint blockade therapies, we are eager to advance the next product candidate from our pipeline of growth factor modulators to potentially address a key mechanism of pre-existing resistance," said Nagesh Mahanthappa, Ph.D., President and CEO of Scholar Rock. "A growing body of evidence strongly implicates elevated TGFβ1 activity as a cause of immunotherapy failure, and we see tremendous potential for SRK-181 to expand the number of patients who could benefit from checkpoint blockade therapies by potently and selectively inhibiting the activation of TGFβ1."

SRK-181 is a fully human antibody designed to bind to, and prevent the activation of, latent TGFβ1 with high affinity and high selectivity, as evidenced by minimal or no binding to latent TGFβ2 and latent TGFβ3 isoforms. Several important factors led to the decision to advance SRK-181 as a clinical development product candidate for the treatment of tumors resistant to checkpoint blockade therapies (CBTs), such as anti-PD1 antibodies. These factors include:

TGFβ signaling has been implicated as a culprit in primary resistance to CBTs in multiple peer-reviewed studies.
Translational data analyses by Scholar Rock highlight the prominent expression of TGFβ1 in many human tumor types, such as bladder cancer, non-small cell lung cancer and melanoma, for which CBTs have either been approved or demonstrated clinical activity in trials.
Clinical correlation and preclinical model data suggest that TGFβ1 excludes effector cell entry into the tumor, thereby limiting immune system access to tumor cells.
Preclinical studies in syngeneic mouse tumor models resistant to CBT show SRK-181-mIgG1 (the murine version of SRK-181), when combined with anti-PD1 antibodies, permitted effector T cell infiltration and expansion into the tumor microenvironment and led to tumor regression or control as well as significant survival benefit.
A 28-day pilot toxicology study of SRK-181 in adult rats showed no observed drug-related toxicity up to a weekly dose of 100 mg/kg for 4 weeks.
Detailed preclinical results for SRK-181-mIgG1 (formerly referred to as SRTβ1-Ab3) were presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 33rd Annual Meeting in November 2018. The poster presented at SITC (Free SITC Whitepaper) can be accessed by visiting the Scholar Rock website at View Source Additional preclinical data for SRK-181-mIgG1 will be presented at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting scheduled to take place March 29 to April 3, 2019 in Atlanta, GA.

About SRK-181
SRK-181 is a highly specific inhibitor of TGFβ1 activation being developed to overcome primary resistance to checkpoint blockade therapies (CBTs). TGFβ1 is the predominant TGFβ isoform expressed in many human tumors, particularly for those tumors where checkpoint therapies are currently approved. Based on analyses of human tumors that are resistant to CBT, TGFβ1 is implicated as a key contributor to exclude immune cell entry into the tumor microenvironment, thereby preventing normal immune function. By overcoming this immune cell exclusion, SRK-181 has the potential to induce tumor regression when administered in conjunction with CBT.

Dong-A ST and Beactica expand their research and license agreement to develop new cancer treatments

On March 12, 2019 Dong-A ST Co., Ltd. (170900: Korea SE), the Korean pharmaceutical company, and Beactica AB, the Swedish drug discovery company, reported an expansion of their research and licensing agreement (Press release, Dong-A ST, MAR 12, 2019, View Source [SID1234535724]). The collaboration – which was initiated in October 2016 – is now expanded with an aim to jointly identify and develop novel small molecules targeting a protein–protein interaction of therapeutic relevance for immuno-oncology. The partnership further builds on Beactica’s unique early-stage lead generation capabilities and Dong-A ST’s strengths in the pharmacological proof of novel target concepts as well as downstream pre-clinical and clinical development of new therapeutic agents.

Under the terms of the additional agreement, Dong-A ST will gain exclusive global rights for the further development and commercialization of compounds discovered. In return, Beactica is eligible to receive research funding as well as milestone payments for certain research, preclinical, clinical and regulatory achievements as well as royalties on commercial sales of the products resulting from the partnership. Beactica is also entitled to a revenue share from any related future licensing activities by Dong-A ST. Full financial details remain undisclosed.

"The collaboration between Dong-A ST and Beactica brings together our complementary strengths and establishes a powerful platform for the discovery and development of next generation anti-cancer therapeutics" said Mr Daesik Eom, Chairman and CEO of Dong-A ST. "Beactica’s capabilities and expertise accelerates the advancement of Dong-A ST’s oncology pipeline and will enhance Dong-A ST’s global competitiveness in the pharmaceutical industry."

"Following recent success in our collaboration we are pleased with Dong-A’s confidence and trust to expand this partnership into new target areas." said Dr Per Källblad, CEO of Beactica. "As a long-term strategic partner we are proud to have delivered valuable contributions to Dong-A’s research and look forward to a continued successful collaboration."

Slide Presentation – 2019 Analyst Day

On March 19, 2019 Ligand presented Analyst Day presentation (Presentation, Ligand, MAR 12, 2019, View Source [SID1234534297]).

Onconova Therapeutics, Inc. to Participate at the 31st Annual ROTH Conference March 17-19, 2019 in Orange County, CA

On March 12, 2019 Onconova Therapeutics, Inc. (NASDAQ: ONTX), a Phase 3-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, with a primary focus on myelodysplastic syndromes, reported that the Company will participate in the 31st Annual ROTH Conference to be held March 17-19, 2019 at the Ritz Carlton Laguna Niguel in Orange County, CA (Press release, Onconova, MAR 12, 2019, View Source [SID1234534298]).

Steven M. Fruchtman, MD, President & CEO, and Mark Guerin, CFO, will attend the conference and be available to meet with investors. Dr. Fruchtman will also participate on a panel to discuss myeloid diseases on Monday, March 18th, from 3:00-4:00p.

Osiris Therapeutics, Inc. Enters Agreement to be Acquired by Smith & Nephew plc

On March 12, 2019 Osiris Therapeutics, Inc. (NASDAQ: OSIR), a regenerative medicine company focused on developing and marketing products for wound care, orthopedics, and sports medicine, reported that it has entered into an agreement and plan of merger with Smith & Nephew plc pursuant to which Smith & Nephew will acquire Osiris for $19.00 per share in cash, a total of approximately $660.5 million in cash (Press release, Osiris Therapeutics, MAR 12, 2019, View Source [SID1234534284]). This offer represents a 37% premium to the company’s 90-day volume-weighted average stock price. The transaction was unanimously approved by the Boards of Directors of both companies.

Peter Friedli, Chairman of the Board and co-founder of Osiris, said, "This is a very good outcome for Osiris’ shareholders. The Board concluded unanimously, after taking into account the requirements needed to take the business to the next level, that entering into this agreement represents the best way to maximize value for our stockholders." Mr. Friedli added, "I am immensely proud of the business we have built from our research into advanced regenerative technologies. I believe Smith & Nephew is the right home for Osiris and will allow our products to reach more customers, helping to restore quality of life for more patients.""This agreement reflects the significant value that the Osiris team has generated for our shareholders under Peter Friedli’s leadership. We believe this transaction will also benefit our customers, employees, and partners," said Samson Tom, President and Chief Executive Officer of Osiris.Completion of the transaction is expected in the second quarter of 2019, pending the successful completion of the tender offer and all other closing conditions. Osiris’ employees are expected to join Smith & Nephew on completion. Until that time, Osiris will continue to operate as a separate and independent company.Cantor Fitzgerald & Co. rendered a fairness opinion to the Board of Directors of Osiris in connection with the transaction. Hogan Lovells US LLP is acting as legal counsel for Osiris.Transaction DetailsUnder the terms of the agreement and plan of merger, Smith & Nephew has formed an acquisition subsidiary, Papyrus Acquisition Corp.

("Purchaser"), that will commence a tender offer no later than April 2, 2019 to purchase all outstanding shares of Osiris for $19.00 per share in cash, and Osiris will file a recommendation statement containing the unanimous recommendation of the Osiris Board that Osiris stockholders tender their shares to Smith & Nephew. Following the completion of the tender offer, Smith & Nephew expects to promptly consummate a merger of Purchaser and Osiris in which shares of Osiris that have not been purchased in the tender offer will be converted into the right to receive the same cash price per share as paid in the tender offer.The tender offer and the merger are subject to customary closing conditions, including the tender of at least a majority of the outstanding Osiris shares on a fully diluted basis and the expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act.

The merger agreement includes customary termination provisions for both Osiris and Smith & Nephew, including a right for either party to terminate if the transactions have not been completed by December 12, 2019. The merger agreement provides that, in connection with the termination of the merger agreement under specified circumstances, including termination by Osiris to accept a superior proposal, Osiris will be required to pay to Smith & Nephew a fee equal to $18,682,450.Smith & Nephew plc (LSE: SN, NYSE: SNN) is making a separate announcement regarding the transaction to its investors today. Annual Report on Form 10-KOsiris intends to file its Annual Report on Form 10-K for the year ended December 31, 2018 on Friday, March 15, 2019.