On November 29, 2021 Fennec Pharmaceuticals Inc., a specialty pharmaceutical company, reported that it expects to receive a Complete Response Letter (CRL) after the PDUFA target action date of November 27, 2021 from the U.S. Food and Drug Administration (FDA) regarding its New Drug Application (NDA) for PEDMARKTM (a unique formulation of sodium thiosulfate), for intravenous administration for the prevention of ototoxicity associated with cisplatin chemotherapy in pediatric patients ≥1 month to 18 years of age with localized, non-metastatic, solid tumors (Press release, Fennec Pharmaceuticals, NOV 29, 2021, View Source [SID1234596197]).

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The FDA has indicated that, following a recent completion of a pre-approval inspection of the manufacturing facility of our drug product manufacturer, deficiencies have been identified. Once the official CRL is received, the Company plans to request a Type A meeting to discuss the deficiencies and steps required for the resubmission of the NDA for PEDMARKTM.

About PEDMARK (A unique formulation of sodium thiosulfate (STS))

Cisplatin and other platinum compounds are essential chemotherapeutic agents for many pediatric malignancies. Unfortunately, platinum-based therapies cause ototoxicity, or hearing loss, which is permanent, irreversible and is particularly harmful to the survivors of pediatric cancer.

In the U.S. and Europe, it is estimated that, annually, more than 10,000 children may receive platinum-based chemotherapy. The incidence of ototoxicity depends upon the dose and duration of chemotherapy, and many of these children require lifelong hearing aids. There is currently no established preventive agent for this type of hearing loss and only expensive, technically difficult, and sub-optimal cochlear (inner ear) implants have been shown to provide some benefit. Infants and young children that suffer ototoxicity at critical stages of development lack speech language development and literacy, and older children and adolescents lack social-emotional development and educational achievement.

PEDMARK has been studied by cooperative groups in two Phase 3 clinical studies of survival and reduction of ototoxicity, The Clinical Oncology Group Protocol ACCL0431 and SIOPEL 6. Both studies have been completed. The COG ACCL0431 protocol enrolled one of five childhood cancers typically treated with intensive cisplatin therapy for localized and disseminated disease, including newly diagnosed hepatoblastoma, germ cell tumor, osteosarcoma, neuroblastoma, and medulloblastoma. SIOPEL 6 enrolled only hepatoblastoma patients with localized tumors.

The Marketing Authorization Application (MAA) for sodium thiosulfate (tradename PEDMARQSI) is currently under evaluation by the European Medicines Agency (EMA). PEDMARK has received Breakthrough Therapy and Fast Track Designation by the FDA in March 2018.

On November 29, 2021 Biofrontera AG (ISIN: DE0006046113) (the "Company") with its wholly owned German subsidiaries, and Biofrontera Inc. (Nasdaq: BFRI), a U.S. subsidiary of the Company, in which it holds less than 100% of the shares, reported that they have reached an out-of-court settlement with DUSA Pharmaceuticals, Inc. ("DUSA") (Press release, Biofrontera, NOV 29, 2021, View Source [SID1234596196]).

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The Company and its defendant subsidiaries were sued in the U.S. by DUSA for alleged patent infringement, unauthorized use of alleged trade secrets, tortious interference with contractual relations and alleged deceptive and unfair trade practices. DUSA has asserted significant damages in this proceeding. In October 2020, the further proceedings, which should now be discontinued, were referred to a jury for a decision.

The settlement was reached based on the following key points: The Company as well as its defendant subsidiaries have agreed to pay DUSA USD 22.5 million in settlement of potential claims. In addition, further mutual claims have been released. Half of the settlement amount is due upon execution of the agreement, thereafter one quarter on each of the first and second anniversaries after execution of the agreement. Of this amount, 50% will be borne by the Company and 50% by Biofrontera Inc.

On November 29, 2021 ImmuPharma PLC (LSE:IMM), the specialist drug discovery and development company, reported that it has signed a 2-year collaboration agreement with Imperial College London (Press release, ImmuPharma, NOV 29, 2021, View Source [SID1234596195]).

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Under the collaboration, Imperial College will provide significant intellectual input and guidance on a number of innovative peptide assets being developed at our R&D subsidiary, ImmuPharma Biotech in Bordeaux.

Dr Tim Franklin, Chief Operating Officer of ImmuPharma, added: "We are all extremely excited to be working with such a world leading academic institute. This union will be invaluable in guiding and progressing our earlier stage product development portfolio, as well as enhancing our intellectual property base."

Dr Sébastien Goudreau, Chief Executive Officer of ImmuPharma Biotech, added: "We are delighted that now with the full support from the new Board for our innovative research programs, we have the opportunity of working with collaboration partners which include world leading academic institutes such as Imperial College London."

On November 29, 2021 Blueprint Medicines Corporation (NASDAQ: BPMC) reported that the company has entered into a definitive agreement under which it will acquire Lengo Therapeutics, a privately held precision oncology company, for $250 million in cash plus up to $215 million in additional potential payments based on the achievement of certain regulatory approval and sales-based milestones (Press release, Bristol-Myers Squibb, NOV 29, 2021, View Source [SID1234596194]).

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The acquisition includes Lengo Therapeutics’ lead compound LNG-451, a potential best-in-class oral precision therapy in development for the treatment of non-small cell lung cancer (NSCLC) in patients with EGFR exon 20 insertion mutations. Preclinical data show LNG-451 potently inhibits all common EGFR exon 20 insertion variants with marked selectivity over wild-type EGFR and off-target kinases. In addition, LNG-451 is highly brain-penetrant and has demonstrated compelling activity in a preclinical intracranial disease model.

Based on these and other preclinical data, Lengo Therapeutics anticipates it will submit an investigational new drug (IND) application for LNG-451 to the U.S. Food and Drug Administration (FDA) in December 2021.

"Our acquisition of Lengo Therapeutics deepens our commitment to advancing precision oncology therapies and specifically expands our opportunity to transform treatment for patients with EGFR-driven lung cancer," said Jeff Albers, Chief Executive Officer of Blueprint Medicines. "The Lengo team has done tremendous work in designing a highly selective therapeutic candidate tailored to the needs of patients with EGFR exon 20 lung cancer, including features with the potential to enable treatment or prevention of brain metastases. With our integrated precision therapy research, development and commercial capabilities, Blueprint Medicines is perfectly positioned to carry forward this compound into the clinic and deliver on our goal to meaningfully advance care for NSCLC patients with EGFR exon 20 insertion mutations."

"With a proven track record of developing and delivering precision therapies for patients with significant medical needs and a compelling lung cancer portfolio, Blueprint Medicines is unique in its abilities to quickly progress LNG-451," said Enoch Kariuki, Chief Executive Officer of Lengo Therapeutics. "From our inception, the Lengo Therapeutics team has focused on generating best-in-class compound profiles, prioritizing those with brain penetration along with high potency and selectivity, like LNG-451. I am incredibly proud of the team for getting us to this point and excited to see the programs continue under Blueprint Medicines’ leadership."

With the addition of LNG-451, Blueprint Medicines will have three investigational compounds, each with best-in-class potential, that cover the majority of all activating mutations in EGFR, the second most common oncogenic driver in NSCLC.1 Approximately 12 percent of activating EGFR mutations are exon 20 insertions and significant medical need remains for patients harboring these mutations, including new treatment options with improved tolerability, combinability and enhanced brain penetration to treat or prevent brain metastases.1

The acquisition also brings additional undisclosed preclinical precision oncology programs and research tools, including a catalog of covalent, highly brain penetrant kinase inhibitors that Blueprint Medicines plans to add to its proprietary compound library to further enable future drug discovery efforts.

Blueprint Medicines anticipates the acquisition will close in the fourth quarter of 2021, subject to certain conditions, including the expiration of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act and other customary conditions.

Goldman Sachs & Co. LLC is acting as financial advisor to Blueprint Medicines and Goodwin Procter LLP is acting as its legal counsel. Centerview Partners LLC is acting as financial advisor to Lengo Therapeutics and Cooley LLP is acting as its legal counsel.

Conference Call Information

Blueprint Medicines will host a live webcast beginning at 8:30 a.m. ET today to discuss the planned acquisition of Lengo Therapeutics. To access the live call, please dial 844-200-6205 (domestic) or 929-526-1599 (international) and refer to conference ID 936793. A webcast of the conference call will be available under "Events and Presentations" in the Investors & Media section of Blueprint Medicines’ website at View Source The archived webcast will be available on Blueprint Medicines’ website approximately two hours after the conference call and will be available for 90 days following the call.

About Blueprint Medicines’ EGFR Development Program

Derived from Blueprint Medicines’ proprietary research platform, BLU-945 and BLU-701 are investigational next-generation EGFR non-covalent tyrosine kinase inhibitors. Both treatments are specifically designed to provide comprehensive coverage of the most common activating and on-target resistance mutations, spare wild-type EGFR and other kinases to limit off-target toxicities and enable a range of combination strategies, and treat or prevent central nervous system metastases. BLU-945 is currently being evaluated in the Phase 1/2 SYMPHONY trial in patients with previously treated EGFR-driven NSCLC (NCT04862780). In addition, Blueprint Medicines plans to initiate a Phase 1/2 trial of BLU-701 in the fourth quarter of 2021.

On November 29, 2021 Kineta, Inc., a clinical stage biotechnology company focused on the development of novel immunotherapies in oncology, reported a presentation describing the Phase 1/2 trial design supporting KVA12.1 for the potential treatment of difficult-to-treat solid tumors at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 36th Anniversary Annual Meeting (Press release, Kineta, NOV 29, 2021, View Source;utm_medium=rss&utm_campaign=kineta-presents-clinical-trial-design-of-kva12-at-sitc [SID1234596193]). Thierry Guillaudeux, PhD, Senior Vice President Immuno-oncology at Kineta, presented a poster outlining the first-in-human clinical trial design KVA 12.1, a novel fully human anti-VISTA antibody, in monotherapy and in combination with an anti-PD1 antibody.

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"Our fully human anti-VISTA antibody, KVA12.1, which binds to a unique epitope has been optimized to reduce the potential risks of severe inflammation . It demonstrates excellent clinical characteristics including an extended pharmacokinetic (PK) profile" said Thierry Guillaudeux, PhD, Senior Vice President Immuno-oncology at Kineta. "We are encouraged by the exceptional preclinical results of KVA12.1 and are eager to enter the clinic with KVA12.1 in the third quarter of 2022."

The Phase 1/2 study will be a multicenter, open label, dose escalation and dose expansion study of intravenous infusion of KVA12.1 as a monotherapy and in combination with a fixed dose of an anti-PD1 antibody in patients with advanced refractory or metastatic solid tumors.

Study objectives detailed from the SITC (Free SITC Whitepaper) poster presentation:

Primary objective: Evaluate the safety, tolerability, Dose Limiting Toxicity (DLT), Maximum Tolerated Dose (MTD) and Identify the Recommended Phase 2 Dose (RP2D) of VISTA-Mab when administered alone and in combination with an anti-PD1 antibody.
Secondary objectives: Further describe i) the PK of KVA12.1; ii) VISTA-Receptor Occupancy; and iii) the anti-tumor activity of KVA12.1 (alone and in combination).
Presentation Details:

Title: KVA 12.1 a novel fully human anti-VISTA antibody clinical trial design in monotherapy and in combination with an anti-PD1 antibody

Date Presented: November 12-13, 2021
Presenter: Thierry Guillaudeux, PhD

Poster: Click on the link below to view the poster:

VISTA Publications – Poster Presentation at SITC (Free SITC Whitepaper) 2021

KVA12.1 is a fully human, optimized IgG1 monoclonal antibody (mAb) that was designed to bind to VISTA through a unique epitope. KVA12.1 drives strong antitumor immune cell activation:

Increases inflammatory monocyte differentiation and activation
Increases HLA-dependent T cell activation
Reduces MDSC-mediated T cell suppression
In preclinical models, KVA12.1 demonstrates strong single agent efficacy in poorly immunogenic "cold tumors" and complementary efficacy when dosed in combination with immune checkpoint inhibitors (ICIs) like PD-1 or CTLA-4. It is well-tolerated with no change in IL6 or TNFα levels, which are responsible for cytokine release syndrome (CRS), in toxicology studies. KVA12.1 is being developed as an intravenous infusion.

KVA12.1 may be an effective immunotherapy for many types of cancer patients including non-small cell lung cancer (NSCLC), colorectal (CRC), renal cell carcinoma (RCC), head and neck squamous cell carcinoma (HNSCC), and ovarian (OC) cancers.