On November 17, 2022 Clovis Oncology reported The FDA has requested that the indication of its PARP inhibitor Rubraca (rucaparib) as second-line maintenance therapy in recurrent ovarian cancer, the company revealed in an SEC filing this week (Press release, Clovis Oncology, NOV 17, 2022, View Source [SID1234624232]).

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The proposed changes to Rubraca’s label would limit its use to only patients harboring tumor BRCA mutations.

If the FDA and Clovis do not reach an agreement over the revisions, the Agency will convene a meeting of the Oncologic Drugs Advisory Committee to re-scrutinize the drug. Clovis is currently considering the FDA’s request, according to the SEC filing.

Rubraca is approved for use in patients in complete or partial response to platinum-based chemotherapy and is also indicated for fallopian tube and primary peritoneal cancer.

This indication is responsible for a "substantial portion" of Clovis’ Rubraca revenue, the company indicated in a 10-Q filing posted early this month.

"We would expect that a limiting of our second line maintenance indication could result in a significant impact on our revenue," the company stated.

The FDA made the revision request on Monday when it met with Clovis via teleconference to discuss overall survival data from the company’s Phase III ARIEL3 clinical trial. Findings from ARIEL3 formed the basis for Rubraca’s regulatory green light in 2018. Complete and final data were submitted in September.

If Clovis concedes to the FDA’s request, it would not be the first time that Rubraca has lost an indication. In June, the company voluntarily withdrew its blockbuster drug from the U.S. market as a treatment option for patients with BRCA-mutation ovarian cancer who have received at least two prior lines of chemotherapy, citing concerns about excess mortality risk in this patient population.

At the time, Clovis said this indication "represents a very small portion of the Company’s total sales" in U.S. and Europe.

Still, times have been tough for the Colorado-based biotech. Earlier this month, amid increasing regulatory scrutiny on Rubraca, Clovis signaled it was at risk of bankruptcy. To stay afloat, the company laid off 115 employees.

Putting the Pressure on PARP Inhibitors

Rubraca is only the latest casualty in the FDA’s intensified probe into safety concerns surrounding PARP inhibitors.

In August, AstraZeneca voluntarily withdrew its Lynparza (olaparib) for the treatment of highly pre-treated patients with advanced ovarian cancer bearing BRCA mutations. The decision follows a subgroup analysis of the Phase III trial SOLO3, which found that treated patients were 33% more likely to die than comparators who received standard chemotherapy.

Meanwhile, GlaxoSmithKline also restricted the use of its PARP inhibitor Zejula earlier this month. Following an FDA request, Zejula as a second-line therapy is now only usable in ovarian cancer patients with deleterious or suspected deleterious germline BRCA mutations. The drug retains its first-line indications in epithelial ovarian, fallopian tube or primary peritoneal cancer.

On November 17, 2022 RAPT Therapeutics, Inc. (Nasdaq: RAPT) ("RAPT" or the "Company"), a clinical-stage, immunology-based biopharmaceutical company focused on discovering, developing and commercializing oral small molecule therapies for patients with significant unmet needs in inflammatory diseases and oncology, reported the pricing of its previously announced underwritten public offering of 4,054,055 shares of its common stock at a price to the public of $18.50 per share. All of the shares of common stock are being offered by RAPT (Press release, RAPT Therapeutics, NOV 17, 2022, https://investors.rapt.com/news-releases/news-release-details/rapt-therapeutics-announces-pricing-public-offering-common-0 [SID1234624228]). Gross proceeds to RAPT from the offering are expected to be $75 million, before deducting underwriting discounts and commissions and estimated offering expenses. In addition, the underwriters have been granted a 30-day option to purchase up to an additional 608,108 shares of common stock at the public offering price, less underwriting discounts and commissions. The offering is expected to close on November 22, 2022, subject to customary closing conditions.

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J.P. Morgan, Evercore ISI, Guggenheim Securities and Cantor are acting as joint book-running managers for the offering.

The offering is being made pursuant to a shelf registration statement, including a base prospectus, filed by RAPT with the Securities and Exchange Commission (the "SEC"), which was declared effective by the SEC on November 16, 2020. The offering may be made only by means of a prospectus supplement and accompanying prospectus. A preliminary prospectus supplement and accompanying prospectus relating to the offering have been filed with the SEC and are available on the SEC’s website at www.sec.gov. When available, electronic copies of the final prospectus supplement and the accompanying prospectus may also be obtained from: J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, by email at [email protected] or by telephone at (866) 803-9204; Evercore Group L.L.C., Attention: Equity Capital Markets, 55 East 52nd Street, 36th Floor, New York, NY 10055, by telephone at (888) 474-0200, or by email at [email protected]; Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Avenue, 8th Floor, New York, NY 10017, by telephone at (212) 518-9544 or by email at [email protected]; or Cantor Fitzgerald & Co., Attention: Capital Markets, 499 Park Avenue, 6th Floor, New York, New York 10022, or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, 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 the registration or qualification under the securities laws of any such state or jurisdiction.

On November 17, 2022 MacroGenics, Inc. (NASDAQ: MGNX), a biopharmaceutical company focused on developing and commercializing innovative antibody-based therapeutics for the treatment of cancer, reported that the U.S. Food and Drug Administration announced the approval of the Biologics License Application (BLA) for teplizumab, an anti-CD3 monoclonal antibody that was previously developed by MacroGenics (Press release, MacroGenics, NOV 17, 2022, View Source [SID1234624227]). Teplizumab was acquired by Provention Bio, Inc. in May 2018 pursuant to an asset purchase agreement.

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"We are very pleased to see the culmination of years of effort by Provention, MacroGenics, and tireless champions in academia and government, with the achievement of the approval of teplizumab," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "We applaud this outcome, which represents an advancement for individuals and their families dealing with the risks and consequences of type 1 diabetes."

Under the agreement, Provention is obligated to pay MacroGenics contingent milestone payments totaling $170 million upon the achievement of certain regulatory approval milestones, including $60 million for the approval of a BLA for a first indication in the United States. In addition, Provention is obligated to make contingent milestone payments to MacroGenics totaling $225 million upon the achievement of certain sales milestones as well as a single-digit royalty on net sales of the product.

Based on MacroGenics’ cash, cash equivalents and marketable securities balance as of September 30, 2022, plus projected and anticipated payments from partners, including timely receipt of the milestone payment from Provention, MacroGenics currently anticipates having a cash runway into late 2024.

On November 17, 2022 The European Organisation for Research and Treatment of Cancer (EORTC), based in Brussels, Belgium, and the King Hussein Cancer Centre (KHCC) in Amman, Jordan reported the signing of an agreement to develop, conduct, and promote translational and clinical cancer research in the Middle East region (Press release, EORTC, NOV 17, 2022, View Source [SID1234624226]). The KHCC will act as the Middle East Co-ordinating Office (MECO) and will provide support to EORTC for its activities. This is the first EORTC collaboration in the region and will form an important part of its effort to develop cancer research in middle-income countries where many patients have not yet had the opportunity to take part in clinical trials.

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Welcoming the signing, EORTC and EORTC Cancer Research Fund (ECRF) Honorary President, HRH Princess Dina Mired of Jordan, said: "The MECO agreement demonstrates how the EORTC stays true to its mission of improving survival and quality of life for all cancer patients. Access to clinical cancer research means a step forward to closing the gap in cancer patient treatment and care. As a Jordanian and Honorary President of the EORTC/ECRF I am proud of the joint initiative between the EORTC and the KHCC."

Dr Lacombe_EORTC_ Dr Mansour_KHCC
The KHCC has successfully contributed to six EORTC clinical trials since 2017 and has a representation of 13 members covering all EORTC research groups. The establishment of the MECO will enable the further development of joint activities with collaborators in the Middle East region. Among the first collaborative activities will be a Clinical Trials Statistics course co-organised by the partners. This will take place in Amman from 15-17 November, taught by an EORTC faculty of statisticians.

Dr Denis Lacombe, EORTC Chief Executive Officer, said: "We are delighted that this collaboration will allow us to expand in the Middle East and bring our expertise to help cancer patients in this part of the world. EORTC is a European organisation, but with an international outlook and a mission to improve the lives of cancer patients worldwide. The agreement with the KHCC brings us a step closer to the achievement of this mission."

Dr Mansour, Chief Executive Officer of the KHCC, said: "We are very excited to start this new era of clinical cancer research in the Middle East, and confident that through the activities of "MECO", we will find synergies with collaborators from this region to conduct cutting-edge research projects and clinical trials that will help us understand how we can embrace and optimize all the advancements taking place in cancer diagnosis and treatment to the benefit of each individual patient, and provide our patients with more opportunities to take part in clinical trials and access newly developed life-saving drugs that may not be available outside the research setting".

On November 17, 2022 KAHR, a clinical-stage biotech company developing a novel, bi-specific CD47x4-1BB targeting immunotherapy that activates innate and adaptive immunity to treat solid tumors and blood cancers, and the Myeloma Investment Fund (MIF), the Multiple Myeloma Research Foundation’s (MMRF) venture philanthropy subsidiary, reported that the MIF has invested in KAHR to explore the potential of DSP107, KAHR’s lead immunotherapy drug candidate, for the treatment of multiple myeloma (Press release, KAHR Medical, NOV 17, 2022, View Source [SID1234624225]).

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"We are thrilled to partner with KAHR to help advance DSP107 as a potential drug candidate for multiple myeloma," said Peter Kosa, Ph.D., Managing Director of the Myeloma Investment Fund. "This investment reinforces our commitment to drive the development of the most innovative treatment approaches for myeloma patients."

"We are excited to have the Myeloma Investment Fund join our syndicate of investors," said Yaron Pereg, Ph.D., Chief Executive Officer of KAHR. "This vote of confidence helps us advance the clinical development of our lead product candidate, DSP107, which is being tested in multiple clinical studies for the benefit of patients who are non-responsive or refractory to existing therapies."

Together with the current investment, KAHR has raised a total of $59 million since June 2021 in private placements supported by aMoon Fund, Flerie Invest AB, Peregrine Ventures, BVF Partners LP, DAFNA Capital Management LLC, Consensus Business Group, Hadasit Bio Holdings Ltd (HBL), Mirae Asset, Shavit Capital, Pavilion Capital, Cancer Focus Fund and Remedii.

About DSP107
DSP107 is a dual-targeting fusion protein that activates innate and adaptive immunity by blocking CD47 on cancer cells and utilizing 4-1BB conditional co-stimulatory activation of T-cells. By binding both cancer cells and immune cells, DSP107 combines checkpoint inhibition with tumor localized immune cell activation to bolster anti tumor immunity. DSP107 binds to and inhibits CD47, an immune checkpoint protein overexpressed in many cancers that enables the tumor to evade immune recognition and attack by macrophages. Simultaneously, when anchored to the tumor, DSP107 binds 4-1BB, a co-stimulatory receptor expressed on T-cells, recruits them to the tumor microenvironment and stimulates their activation. These activities result in targeted macrophage and T-cell mediated immune activation and tumor destruction.

DSP107 has demonstrated an excellent safety profile, no binding to red blood cells, biological activity, and high disease control rates in a Phase I trial of patients with advanced solid tumors. DSP107 is also being tested in combination with Atezolizumab in a Phase I/II trial in patients with advanced solid tumors and in combination with standard of care therapies for relapsed/refractory AML and MDS patients in a Phase Ib study.