Blueprint Medicines to Expand Precision Therapy Leadership in Lung Cancer with Acquisition of Lengo Therapeutics

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.

Kineta Presents Phase 1/2 Clinical Trial Design of KVA12.1 at the Society for Immunotherapy of Cancer (SITC) 36th Annual Meeting

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.

Sorrento Publishes an Abivertinib Teaser Entitled “Abivertinib – a Franchise Oral Therapeutic For Cancer, Covid-19 And Autoimmune Diseases

On November 29, 2021 Sorrento Therapeutics, Inc. (Nasdaq: SRNE, "Sorrento") reported the publication of a Teaser titled "Abivertinib – a Franchise Oral Therapeutic for Cancer, COVID-19 and Autoimmune Diseases" ("Abivertinib Teaser"). Sorrento intends to use the Abivertinib Teaser to engage in discussions with interested third parties in the pharmaceutical industry (Press release, Sorrento Therapeutics, NOV 29, 2021, View Source [SID1234596192]).

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The key highlights of the Abivertinib Teaser are outlined below:

Abivertinib for COVID-19 (Two Phase 2 trials Completed)
100 mg once-a-day oral capsule for hospitalized COVID-19 patients
US trial (N=96) and Brazil trial (N=400)
For Severe Ordinal Scale (OS) Category 5 COVID-19 Patients ("At-Risk Group") identified to be beneficial with Abivertinib treatment at Day 28 (D28):

Abivertinib reduced the risk of death or respiratory failure:

by 48% in US trial (death or respiratory failure: 21.7% in the Abivertinib group vs. 41.7% in the placebo plus Standard of Care (SoC) control group)
by 45% in Brazil trial (death or respiratory failure: 30.4% Abivertinib vs. 55.6% placebo plus SoC controls)

Abivertinib reduced the ICU stay:

by 2 days in the US trial (8.6 days average stay in ICU in Abivertinib group vs. 10.6 days in placebo plus SoC control group)

Abivertinib for Cancer Indications
NSCLC (Pivotal Trial: N=229) – Among 209 response evaluable NSCLC patients who developed resistance to first line Tyrosine Kinase Inhibitors (TKIs):

93.3% (n/N: 195/209) subjects achieved tumor shrinkage at target lesions
57.4% (n/N: 120/209) subjects achieved the best ORR (confirmed + unconfirmed
PR)
52.2% (n/N: 109/209) subjects achieved confirmed PR1
24.9 months OS
B-Cell Lymphoma (Phase 1/2 Trial) (as of 08/28/2020)

63.6% ORR (n/N: 14/22)
95.5% DCR (n/N: 21/22)
19.7 Months PFS
Abivertinib – A Broad Pipeline for Cancer, COVID-19 and Autoimmune Diseases ($61B Market)

Celsion Corporation Invited to Present Poster at Cytokine-Based Cancer Immunotherapies Summit

On November 29, 2021 Celsion Corporation (NASDAQ: CLSN), a clinical-stage development company focused on DNA-based immunotherapy and next-generation vaccines, reported that Khursheed Anwer, Ph.D., executive vice president and chief science officer, will be making a presentation on the Company’s GEN-1 interleukin 12 (IL-12) immunotherapy program at the Cytokine-Based Cancer Immunotherapies Summit being held in Boston on November 30 to December 2, 2021 (Press release, Celsion, NOV 29, 2021, View Source [SID1234596191]). Dr. Anwer’s presentation, titled "A Non-Viral Gene Therapy Approach to IL-12 Delivery for The Treatment of Cancer," will be delivered on December 2 at 8:10 a.m. Eastern time. The Company was invited to submit a poster presentation which aligns with Dr. Anwer’s oral presentation on the GEN-1 IL-12 program. The poster presentation will contain a subset of his presentation slides. Dr. Anwer will also be participating in two panel discussions.

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In his presentation, Dr. Anwer will be discussing how local delivery of IL-12 without significant systemic toxicity is feasible with a non-viral gene therapy approach that involves administration of an IL-12 plasmid with a synthetic DNA delivery system (GEN-1). Dr. Anwer will also be discussing how weekly intraperitoneal administration of GEN-1 yields durable increases in IL-12 and IFN-, and why repeated weekly administration of GEN-1 in combination with standard chemotherapy remodels the tumor immune environment to favor immune stimulation over immune suppression.

"We are pleased that the Cytokine-Based Cancer Immunotherapies Summit is recognizing Celsion’s leadership for and potential efficacy of cytokines as an immunotherapy for the treatment of serious malignancies," said Michael H. Tardugno, chairman, president and chief executive officer of Celsion. "Results from the Company’s Phase I Study of GEN-1 in advanced ovarian cancer is attracting the interest of leading researchers in the field of immunotherapy."

Dr. Anwer will also participate in two panel discussions:

On December 1 at 8:30 a.m. Eastern time titled, "What Do We Know & Where Do We Want to Go?"
On December 2 at 11:30 a.m. Eastern time titled "Side Effects – Mitigating Against Hypotension + Fever With Immune-Stimulating Agents (NK Cell Engagers, PD-1s, Cytokines, T-Cell Engagers) = Cytokine Release Syndrome (CRS)?"
About GEN-1 Immunotherapy

GEN-1, designed using Celsion’s proprietary TheraPlas platform technology, is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system that enables cell transfection followed by persistent, local secretion of the IL-12 protein. IL-12 is one of the most active cytokines for the induction of potent anticancer immunity acting through the induction of T-lymphocyte and natural killer (NK) cell proliferation and maturation. The company previously reported positive safety and encouraging Phase I results with GEN-1 given as monotherapy or a combination therapy in patients with advanced peritoneally metastasized primary or recurrent ovarian cancer, and recently completed a Phase Ib dose-escalation trial (OVATION 1 Study) of GEN-1 in combination with carboplatin and paclitaxel in patients with newly diagnosed ovarian cancer. GEN-1 in combination with neoadjuvant chemotherapy is the subject of the ongoing randomized Phase II OVATION 2 Study in subjects with advanced-stage ovarian cancer (Stage III/IV), with enrollment now exceeding 75% and full enrollment targeted by the first half of 2022.

BioMarin to Participate in Two Upcoming Virtual Investor Conferences

On November 29, 2021 BioMarin Pharmaceutical Inc. (NASDAQ: BMRN) reported that management will participate in two upcoming virtual investor conferences (Press release, BioMarin, NOV 29, 2021, View Source [SID1234596190]). An audio webcast of the presentations will be available live. You can access the webcasts at: View Source An archived version of the remarks will also be available through the Company’s website for a limited time following the conference.

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