On December 30, 2021 Blueprint Medicines Corporation (NASDAQ: BPMC) reported that the company has successfully completed its previously announced acquisition of Lengo Therapeutics and 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 (Press release, Blueprint Medicines, DEC 30, 2021, View Source [SID1234597852]). An investigational new drug (IND) application for LNG-451 was submitted to the U.S. Food and Drug Administration (FDA) by Lengo Therapeutics in December 2021.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The acquisition of Lengo Therapeutics and its lead candidate LNG-451 enables Blueprint Medicines to expand our pipeline in lung cancer and harness our experience and expertise to advance precision oncology therapies for the patients who need them," said Fouad Namouni, M.D., President of Research & Development. "I want to thank the Lengo Therapeutics team, again for their work to advance the highly selective therapeutic candidate LNG-451, but also for completing the IND submission with a continued sense of urgency. Pending FDA clearance of the application, we plan to advance LNG-451 into the clinic in the first quarter of 2022."

As previously disclosed, under the terms of the agreement, Blueprint Medicines acquired Lengo Therapeutics 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.

On December 30, 2021 BeyondSpring Inc. (the "Company" or "BeyondSpring") (NASDAQ: BYSI), a global biopharmaceutical company focused on the development of innovative cancer therapies, reported its financial results for the third quarter ended September 30, 2021, and provided an update on recent corporate events (Press release, BeyondSpring Pharmaceuticals, DEC 30, 2021, View Source;utm_medium=rss&utm_campaign=beyondspring-announces-third-quarter-2021-financial-results-and-provides-a-corporate-update [SID1234597851]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"In the third quarter, we continued to move forward in developing plinabulin’s potential as a ‘pipeline in a drug’ for patients in need. We are developing a wealth of clinical data showing plinabulin’s dual benefit as an anti-cancer agent, shown with OS benefit in Dublin-3 study, with additional benefit in preventing CIN, which we believe will support the important role of plinabulin as a versatile cancer treatment option, and potentially, as a ‘cornerstone’ therapy in IO combinations," said Dr. Lan Huang, co-founder, chairwoman and chief executive officer of BeyondSpring.

"We look forward to executing on our plans for the potential commercial launch of plinabulin in CIN, our first indication in China, where we are excited to work with a leading oncology company, Hengrui, in the commercialization and co-development of plinabulin. Our discussions will continue with the U.S. FDA regarding the potential regulatory pathway for CIN in the U.S. market. At the same time, we are very focused on preparing for our NDA filing for plinabulin in NSCLC. Based on discussions with regulatory agencies in the U.S. and in China, we now anticipate submitting our NDA in the 2H 2022. The year ahead will be very busy and significant for BYSI, and we remain dedicated to enabling plinabulin to achieve its full potential and to bringing added value to the treatment of cancer patients," concluded Dr. Huang.

Recent Clinical and Corporate Highlights

Presented positive final Phase 3 DUBLIN-3 data with the plinabulin/docetaxel combination versus docetaxel alone in 2nd/3rd line non-small cell lung cancer patients with EGFR Wild Type at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2021 Congress
The combination showed superior efficacy benefit in overall survival, progression-free survival (PFS), overall response rate (ORR), and significant reduction of grade 4 neutropenia vs. docetaxel alone.
The combination also demonstrated superior and clinically meaningful Quality of Life benefit: 18.4% of relative improvement in Q-TWiST (Quality-adjusted Time Without Symptoms of Disease and Toxicity).
Presented new data on plinabulin from its Chemotherapy-Induced Neutropenia (CIN) prevention program in three posters at the ESMO (Free ESMO Whitepaper) 2021 Congress (titles below):
Severe Neutropenia (Grade 4, Gr4N) as a Population-Based Predictor for Adverse Clinical Outcome of Chemotherapy Induced Neutropenia (CIN)
Prediction of Febrile Neutropenia (FN), Hospitalization (Hosp) Rates, and Infection (Inf) Rates in Chemotherapy-Induced Neutropenia (CIN) Patients (pts) Treated with the Plinabulin and Pegfilgrastim Combination (Plin+Peg) using a Meta-Analysis (MA)-based Tool
Impact of Adding Plinabulin to Pegfilgrastim for the Prevention of Chemotherapy Induced Neutropenia (CIN), on Patient Quality of Life (QoL)
Announced first patient treated in its Phase 2 study of plinabulin in combination with nivolumab + ipilimumab in patients in extensive-stage small-cell lung cancer (SCLC) who progressed after at least one platinum-based chemotherapy regimen and checkpoint inhibitors
The investigator-initiated study (IIT) is being conducted through the Big Ten Cancer Research Consortium in 7 U.S. clinical centers.
In Phase 1 study, plinabulin combination with nivolumab + ipilimumab had ORR of 43% in SCLC patients who had progressed on platinum and checkpoint inhibitors (presented at ASCO (Free ASCO Whitepaper) 2021).
Announced new patient-derived (PDX) cancer model data for plinabulin monotherapy, which further supports the positive clinical data in the treatment of SCLC
At the 2021 AACR (Free AACR Whitepaper)-NCI-EORTC virtual international conference on molecular targets and cancer therapeutics, the Company presented additional preclinical data in plinabulin monotherapy activity in PDX models in glioblastoma multiforme, bladder cancer, gastric cancer, sarcoma, triple-negative breast cancer, and SCLC, with IC70 at 35 nM in SCLC.
Entered into an exclusive commercialization and co-development partnership between Jiangsu Hengrui Pharmaceuticals Co., Ltd. ("Hengrui") and Wanchunbulin, BeyondSpring’s China subsidiary, for plinabulin in Greater China
Hengrui, a leading oncology R&D and commercial company in China, has exclusive commercialization and co-development rights to all indications for plinabulin. Hengrui will pay all commercialization costs for all indications of plinabulin, and half of clinical development costs for new indications.
Wanchunbulin will supply plinabulin, retaining manufacturing rights. Wanchunbulin will receive all proceeds from sales of plinabulin products and pay Hengrui a pre-determined percentage of such sales.
Wanchunbulin received 200M RMB (est. US$30M) upfront, and will be eligible to receive up to 1.1B RMB (est. US$170M) in regulatory and sales milestones.
NDA for plinabulin-G-CSF combination in CIN Prevention under review in China; received complete response letter from U.S. FDA, with plans for further discussions with FDA on future regulatory pathway
Changes to the Company’s Board of Directors
Mark Santos, RPh joined the Company’s Board of Directors in November 2021. Mr. Santos has more than 30 years of experience in healthcare industries. He is SVP of Pharma Strategy & Contracting at OneOncology and past President of ION Solutions, the leading group purchasing organization (GPO) in the U.S. He serves as a board member for the American Cancer Society (South Texas Center), NY Cancer Foundation, and Leukemia Texas Foundation, among other organizations.
On December 22, 2021, Dr. Ravi Majeti resigned from the Board.
On July 27, 2021, Dr. Quanqi Song resigned from the Board of Directors and the Audit Committee, and Brendan Delaney, an independent Director, was appointed to the Audit Committee.
Upcoming Milestones

1H 2022: expected regulatory update for CIN indication in China; continuing discussions with FDA on regulatory pathway for CIN in the U.S.
2H 2022: NDA Submission for plinabulin in NSCLC
2H 2022: Phase 2 data from the Big Ten Cancer Research Consortium, IIT study expected in plinabulin + nivolumab + ipilimumab in platinum and checkpoint inhibitor-resistant SCLC.
2H 2022: Preliminary Phase 1 data and plinabulin immune mechanism data from the MD Anderson Cancer Center, IIT study expected in plinabulin + PD-1/PD-L1 inhibitors + radiation in patients with seven cancer types.
Third Quarter Financial Results

Research and development ("R&D") expenses were $8.5 million for the quarter ended September 30, 2021, compared to $8.6 million for the quarter ended September 30, 2020. The decrease was primarily due to lower clinical development expenses, which were partially offset by higher personnel and non-cash stock-based compensation expenses.
General and administrative ("G&A") expenses were $10.2 million for the quarter ended September 30, 2021, compared to $6.7 million for the quarter ended September 30, 2020. The $3.5 million increase was primarily due to higher personnel costs and expenses associated with plinabulin pre-commercialization activities.
Net loss attributable to the Company was $18.4 million for the quarter ended September 30, 2021, compared to $14.5 million for the quarter ended September 30, 2020.
As of September 30, 2021, the Company had cash, cash equivalents, and short-term investments of $91.6 million. The Company believes it has sufficient cash to support its ongoing clinical programs over the next year, including its immuno-oncology pipeline.
Year-to-Date Financial Results

R&D expenses were $31.1 million for the nine-month period ended September 30, 2021, compared to $33.4 million for the nine-month period ended September 30, 2020. The $2.3 million decrease was primarily due to lower clinical development expense, partially offset by higher personnel and professional services expenses, as well as PDUFA NDA application fees to FDA.
G&A expenses were $25.7 million for the nine-month period ended September 30, 2021, compared to $12.2 million for the nine-month period ended September 30, 2020. The $13.5 million increase was primarily due to higher personnel costs, non-cash stock-based compensation expense and pre-commercialization expenses for plinabulin.
Net loss attributable to the Company was $54.7 million for the nine-month period ended September 30, 2021, compared to $43.4 million for the nine-month period ended September 30, 2020.

On December 29, 2021 The Janssen Pharmaceutical Companies of Johnson & Johnson reported the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) seeking approval of teclistamab for the treatment of patients with relapsed or refractory (R/R) multiple myeloma (Press release, Johnson & Johnson, DEC 29, 2021, View Source [SID1234597842]). Teclistamab is an investigational, off-the-shelf, T-cell redirecting, bispecific antibody targeting both B-cell maturation antigen (BCMA) and CD3.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Despite all the gains that have been made in treating multiple myeloma, the unmet need still remains very high. Our relentless pursuit of treatments for this disease continues with the same sense of urgency that we have always had," said Peter Lebowitz, M.D., Ph.D., Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC. "We look forward to working with the FDA in their review of our teclistamab submission."

The BLA submission for teclistamab is supported by data from MajesTEC-1 (NCT04557098, NCT03145181), an open-label, multicenter clinical trial evaluating the safety and efficacy of teclistamab in adults with R/R multiple myeloma. In the study, investigators assessed efficacy outcomes, including overall response rate, very good partial response and complete response using International Myeloma Working Group (IMWG) criteria, as well as the safety profile of teclistamab. Updated MajesTEC-1 data were recently presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting.1

"The deep expertise, creativity and persistence of the entire Janssen R&D organization enabled the expeditious advancement of teclistamab for multiple myeloma," said Mathai Mammen, M.D., Ph.D., Global Head, Janssen Research & Development, Johnson & Johnson. "Today’s submission is another important step in our commitment to bring to patients truly transformational medicines that profoundly impact their health."

Multiple myeloma is an incurable blood cancer that affects white blood cells called plasma cells, which are found in the bone marrow and normally make antibodies which fight infection.2,3 When these plasma cells become malignant and develop into multiple myeloma, these myeloma cells proliferate and replace normal cells in the bone marrow. In 2021, it is estimated that nearly 35,000 people will be diagnosed and more than 12,000 will die from this disease in the U.S.4 While some patients with multiple myeloma initially have no symptoms, many patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.5

About Teclistamab
Teclistamab is an investigational, off-the-shelf, T-cell redirecting, bispecific antibody targeting both BCMA (B-cell maturation antigen) and CD3, the T-cell receptor. BCMA is expressed at high levels on multiple myeloma cells.6,7,8,9,10 Teclistamab redirects CD3-positive T-cells to BCMA-expressing myeloma cells to induce killing of tumor cells.5

Teclistamab is currently being evaluated in several monotherapy and combination studies. In 2020, the European Commission and the U.S. FDA each granted teclistamab Orphan Drug Designation for the treatment of multiple myeloma. In January 2021 and June 2021, teclistamab received a PRIority MEdicines (PRIME) designation by the European Medicines Agency (EMA) and Breakthrough Therapy Designation (BTD) by the U.S. FDA, respectively. PRIME offers enhanced interaction and early dialogue to optimize drug development plans and speed up evaluation of cutting-edge, scientific advances that target a high unmet medical need.11 The U.S. FDA grants BTD to expedite the development and regulatory review of an investigational medicine that is intended to treat a serious or life-threatening condition and is based on preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy.12

On December 29, 2021 Antengene Corporation Limited ("Antengene" SEHK: 6996.HK), a leading innovative, global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class medicines for cancer and other life-threatening diseases, reported that the first patient has been dosed in the Phase Ib/II, open-label multi-center, REACH trial to evaluate ATG-016 (eltanexor) monotherapy in subjects with advanced solid tumors including those with genetic mutations (such as K-ras or p53) or a viral association (such as Epstein Barr Virus (EBV) and Human Papilloma Virus (HPV). Enrollment in the study is already underway (Press release, Antengene, DEC 29, 2021, View Source [SID1234597838]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The opening of the REACH trial is a very important milestone for Antengene. As the second study of ATG-016 to be conducted in mainland China, it highlights our approach of running our own, complementary, additional studies in China on partnered products," said Jay Mei, M.D., Ph.D, Founder and CEO of Antengene. "Furthermore, this study underscores Antengene’s commitment to focusing our clinical development efforts on diseases that are particularly prevalent in China versus the US," continued Dr. Mei.

ATG-016/eltanexor and other SINE (Selective Inhibitor of Nuclear Export) compounds inhibit the nuclear chaperone protein called Exportin 1 (XPO1) that helps cancers grow by removing tumor suppressor proteins from the nucleus. ATG-016 is an orally-active, highly-specific next-generation XPO1 inhibitor with an improved pharmacological profile and reduced brain penetration versus the first novel SINE compound, ATG-010/selinexor. These attributes can potentially enable more frequent dosing and a better tolerated dosing regimen. ATG-016 demonstrated preliminary anti-tumor activity in a Phase I study in advanced solid tumors and hematologic malignancies. SINE compounds also inhibit replication of viruses that utilize XPO1 machinery. In preclinical studies, ATG-016 demonstrated an inhibitory effect on the growth of cancer induced by viruses such as EBV and HPV.

"The REACH study is designed to evaluate the safety, pharmacokinetics and preliminary efficacy of ATG-016/eltanexor monotherapy in patients with progressive or resistant disease, building on promising, published Phase I results. With 70% of cancer patients remaining as non-responders or progressing after initial response, Antengene has prioritized the development of treatments for advanced or resistant cancers," said Kevin Lynch, M.D., Antengene’s Chief Medical Officer. "We remain grateful to all of the healthcare professionals, scientists, patients, and families involved with Antengene’s clinical studies," continued Dr. Lynch.

About the REACH Trial

The REACH trial is a multicenter, open-label Phase Ib/II exploratory trial comprising a dose-escalation portion and dose-expansion portion. The initial dose-escalation of ATG-016 will be conducted in patients with advanced solid tumors, to determine the maximum-tolerated dose (MTD), recommended Phase II dose (RP2D), and biologically effective dose of ATG-016. Then the study will proceed to the dose-expansion portion and initiate the Phase II study in patients with relapsed or metastatic penile squamous cell carcinoma or Stage IV nasopharyngeal carcinoma (endemic tumors in China and southeastern in China) to further assess the efficacy and safety of ATG-016 monotherapy. In the Phase II study, investigators will evaluate tumor responses every six weeks using the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST1.1).

About the SINE Compounds

SINE (Selective Inhibitor of Nuclear Export) compounds are inhibitors of the major nuclear export protein Exportin 1 (XPO1). Currently, there are three oral SINE compounds, ATG-010 (selinexor), ATG-016 (eltanexor), and ATG-527 (verdinexor), under clinical development. Antengene has an exclusive license from Karyopharm Therapeutics Inc. ("Karyopharm") to develop and commercialize these compounds in certain APAC markets.

About ATG-010/Selinexor/ XPOVIO

ATG-010/selinexor (XPOVIO) is the first-generation SINE compound. Karyopharm developed and secured approval by the US FDA for the treatment of relapsed/refractory multiple myeloma (RRMM) and relapsed, refractory diffuse large B-cell lymphoma.

Antengene secured approval of ATG-010 in South Korea and China through a priority review process. Antengene is conducting 10 additional studies with ATG-010 in mainland China (3 in collaboration with Karyopharm).

About ATG-016/Eltanexor

Karyopharm is conducting a Phase I/II trial for eltanexor in subjects with Myelodysplastic syndrome (MDS).

Antengene is also evaluating ATG-016/eltanexor in the HATCH study, a Phase I/II monotherapy, registration-track study in high-risk MDS patients who have failed hypomethylating agents.

On December 29, 2021 Bio-Thera Solutions, Ltd. (SH: 688177), a commercial-stage pharmaceutical company, reported that dosing has begun in Phase I clinical study to compare the pharmacokinetics and safety of BAT6026, an agonist monoclonal antibody targeting OX40 in cancer patient volunteers (Press release, BioThera Solutions, DEC 29, 2021, View Source [SID1234597833]). BAT6026 was discovered using Bio-Thera’s proprietary IDEAL (Intelligent Design and Engineered Antibody Libraries) platform. The Antibody Dependent Cellular Cytotoxicity (ADCC) of BAT6026 has been enhanced through significant afucosylation of BAT6026.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"OX40 is an important immune-oncology and autoimmune drug target. We are very excited about the preclinical profile of BAT6026, both as a single agent and in combination with other immune-oncology (IO) agents." said Dr. Jin-Chen Yu, SVP, Bio-Thera Solutions. "BAT6026 is one of multiple IO assets in our pipeline targeting tumor infiltrating regulatory T cells (Tregs) through enhanced ADCC effects. We plan to explore combinations of BAT6026 with BAT1308, our novel PD-1 antibody, to treat a broad range of cancers."

The Phase 1, multicenter, open-label, dose-escalation clinical trial of BAT6026 is designed to assess the safety and tolerability of BAT6026 as a single agent. The study is expected to enroll subjects with advanced solid tumor. Key objectives in the study include determining maximum tolerated dose, pharmacokinetics and preliminary anti-tumor activity. Disease-specific expansion cohorts will be enrolled at the maximally tolerated or biologically relevant dose.

About IDEAL Platform

Bio-Thera Solutions has developed a proprietary fully synthetic human antibody discovery platform called IDEAL, which stands for Intelligent Design and Engineered Antibody Libraries Platform. The CDR-H3 of our novel innovative antibodies is designed based on over 100,000 natural human antibody sequences. Our IDEAL library has an overall diversity of CDR-H3 over 3E+11. Fixed clinically proven frameworks are utilized to increase the odds of development. A universal affinity maturation library is used for all candidates. A fast high-throughput screening platform is employed.