On June 18, 2020 BridgeBio Pharma, Inc. (NASDAQ: BBIO), a clinical-stage biopharmaceutical company focused on genetic diseases, reported that it has entered into a collaboration agreement with Johns Hopkins University to support the translation of academic innovations in genetically driven diseases with a goal of clinical development and potential commercialization to reach patients in need (Press release, BridgeBio, JUN 18, 2020, View Source [SID1234576228]).

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"We are privileged to establish a framework for collaboration with Johns Hopkins University, an institution that has pioneered our understanding of Mendelian disease. Our hope is that this relationship will allow us to build on the significant advances being made in Johns Hopkins’ labs and support work to translate them as quickly and as safely as possible into meaningful medicines for patients in need," said BridgeBio CEO and founder Neil Kumar, Ph.D.

BridgeBio has a deep interest in understanding where great science is occurring and determining how it can support translating academic findings into treatments for patients, including by helping advance the important discoveries in genetic drivers of specific diseases made at Johns Hopkins. The company is focused on building relationships with academic partners to smooth and speed up the transition from the lab to the patient.

BridgeBio will focus on opportunities to support the incredible, early-discovery research around genetically validated targets underway at Johns Hopkins. Where possible, BridgeBio will invest heavily in programs to accelerate promising genetic-disease therapies to the clinic, from gene therapy to small molecule. It will lend its expertise to science designed to help develop a promising molecule or approach into a viable preclinical program, including medicinal chemistry for small-molecule hit optimization, strategies to modify or formulate a potential biologic therapy or approaches for testing non-optimized viral vectors. Additionally, BridgeBio may conduct proof-of-concept studies for lead therapeutic compounds in relevant mammalian models.

BridgeBio seeks to revolutionize partnerships between drug development companies and biomedical research institutions by moving away from one-off interactions and building long-term partnerships based on trust, engagement, science and respect. The company is committed to acting responsibly with academic investigators who are on the front lines of understanding the mechanisms of genetically driven diseases and have great insights into how these diseases may be treated.

On June 18, 2020 BridgeBio Pharma, Inc. (NASDAQ: BBIO), a clinical-stage biopharmaceutical company focused on genetic diseases, reported that it has entered into a strategic collaboration with the University of Florida to translate research in genetically driven disease towards clinical development and potential commercialization (Press release, BridgeBio, JUN 18, 2020, View Source [SID1234576227]). The partnership combines University of Florida’s prowess in studying genetically driven disease, including its capabilities in gene therapy, with BridgeBio’s expertise in efficiently advancing therapeutics from the academic laboratory through preclinical studies and into human testing.

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BridgeBio believes that, too often, promising research in academia sits on the shelf without partners to move it forward. The company’s mission is to bring as much of that research forward as possible, by focusing on establishing partnerships with leading institutions in the hopes of translating research into life-saving therapies.

"The scientists at University of Florida are recognized as leaders in research dedicated to genetically driven diseases, especially in the area of gene therapy. We are proud and eager to collaborate with them to push potential therapies forward for patients in need," said BridgeBio CEO and founder Neil Kumar, Ph.D.

BridgeBio will provide sponsorship to select research programs around diseases with a genetic basis, including gene therapies and large and small molecules. The company will provide guidance for sponsored programs around medicinal chemistry for small-molecule hit optimization, strategies to modify or formulate a potential biologic therapy or approaches for testing non-optimized viral vectors. BridgeBio may conduct proof-of-concept studies for lead therapeutic compounds in relevant mammalian models.

"Great academic research scientists at the University of Florida have produced groundbreaking research, and through a partnership with BridgeBio we hope to turn more of that research into approved medicines for patients," said Jim O’Connell, assistant vice president for commercialization at University of Florida. "BridgeBio has shown it understands the complexities in advancing gene therapies toward clinical development for patients in need – regardless of the size of an indication. We are encouraged by the company’s ability to advance multiple programs in parallel and commitment to patient communities. It is gratifying to see a drug development company take inspiration from the work that we are doing."

BridgeBio seeks to revolutionize partnerships between drug development companies and biomedical research institutions by moving away from one-off interactions and building long-term partnerships based on trust, engagement, science and respect. The company is committed to acting responsibly towards the academic investigators who are on the front lines of understanding the mechanisms of genetically driven diseases and have great insights into how these diseases may be treated.

On June 18, 2020 Cancer Prevention Pharmaceuticals, Inc. (CPP), a private biotech company developing novel therapeutics to prevent cancer and other diseases,reported that it has submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for CPP-1X/sul for treatment of adults with familial adenomatous polyposis (FAP) (Press release, Cancer Prevention Pharmaceuticals, JUN 18, 2020, https://www.canprevent.com/wp-content/uploads/2020/06/MAA-Submission-Press-Release-FINAL-2020-06-18.pdf [SID1234563866]).

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FAP is a rare genetic disease that if left untreated progresses to colorectal cancer in nearly 100% of patients. The clinical development of CPP-1X/sul was designed to establish this fixed dose combination product as a potential pharmaco-preventive drug treatment specifically for FAP patients.

"The MAA submission for our lead drug candidate, CPP-1X/sul, represents a significant milestone for FAP patients and their families," said CPP CEO Jeff Jacob. "For most FAP patients, current medical practice involves a lifetime of periodic monitoring as well as highly invasive surgical procedures. If approved, CPP-1X/sul could provide an alternative to surgery for some patients, significantly improving their quality of life."

CPP-1X/sul has received an orphan medicinal product designation for FAP by the European Commission following a favorable assessment provided by the EMA’s Committee for Orphan Medicinal Products. Among the potential benefits arising from the designation are 10 years of orphan market exclusivity as well as eligibility of the product being assessed and approved centrally in the European Union leading to grant of a marketing authorization, which is valid in all Member States of the EU and the European Economic Area.

CPP also plans to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration this month seeking accelerated approval for CPP-IX/sul for the same indication.

About CPP-1X/sul
CPP-1X/sul is a combination of CPP-1X (eflornithine) and sulindac (CPP-1X/sul). In a clinical trial in patients with large bowel polyps, the CPP-X/sul combination prevented > 90% subsequent pre-cancerous sporadic adenomas versus placebo. Based on the close biologic similarities with FAP, a phase 3 pivotal trial compared this same combination to each drug alone (FAP-310).

"With up to four years of treatment, the combination appears to greatly delay the need for major surgeries in the colon, rectum or surgical pouch. We hope that this new drug regimen will soon be available as an adjunct in the management of FAP patients facing large bowel surgery," said Dr. Alfred Cohen, Chief Medical Officer of CPP.

The Phase 3, pivotal FAP-310 trial of CPP-1X/sul enrolled 171 FAP patients at 17 research institutes in the U.S., Canada, and Europe. It was the largest ever prospective, controlled study performed in FAP and treated patients for up to 48 months, much longer than any other clinical trial in this population. The study was designed to determine if CPP-1X/sul is superior to sulindac or eflornithine as single agents in delaying time to the first occurrence of any FAPrelated event, such as surgical removal of the colon, rectum, surgical pouch, duodenum and/or high-risk adenomas. The trial design included FAP patients with varying lower and upper GI disease. CPP-1X/sul did not demonstrate statistical significance in outperforming the single agents in the overall population; however, further analysis of the data showed key differential effects of the agents in the lower vs upper GI anatomy. Focusing on lower GI anatomy (patients with an intact colon, retained rectum or surgical pouch), the data showed statistically significant benefit for CPP-1X/sul vs both single agents (p≤0.02) in delaying surgical events in the lower GI for up to 4 years. Also, the safety profile of the combination did not significantly differ from that already known for the single agents to support the overall safety assessment of the fixed combination product for long-term therapeutic use.

On June 18, 2020 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biotechnology company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported that its marketing authorization application (MAA) for BRUKINSA (zanubrutinib) for the treatment of patients with Waldenström’s macroglobulinemia (WM) who have received at least one prior therapy or as first-line treatment for patients unsuitable for chemo-immunotherapy has been validated for regulatory review by the European Medicines Agency (EMA) (Press release, BeiGene, JUN 18, 2020, View Source [SID1234561430]).

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"This is our first submission to the EMA and the first for WM, marking a significant milestone for BRUKINSA, which has demonstrated efficacy and clinically meaningful improvements in safety and tolerability in patients with WM compared to the first-generation BTK inhibitor, ibrutinib, in our head-to-head ASPEN trial. BRUKINSA has been approved in the U.S. and China in other indications, and we are excited to continue its broad, global development program to help patients with B-cell lymphomas," said Jane Huang, M.D., Chief Medical Officer, Hematology at BeiGene. "WM is typically a disease of older individuals, and we are hopeful that BRUKINSA’s cardiovascular safety advantages over ibrutinib may help it become a preferred treatment option for patients in Europe with WM."
Clinical data in the MAA include the Phase 3 randomized, open-label, multicenter ASPEN clinical trial (NCT03053440) that evaluated zanubrutinib versus ibrutinib in patients with relapsed/refractory (R/R) or treatment-naïve (TN) WM which was recently presented at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual Scientific Program and the 25th European Hematology Association (EHA) (Free EHA Whitepaper) Congress. The safety package in the MAA included pooled safety data from 779 patients with B-cell malignancies treated with BRUKINSA in six clinical trials.
About Waldenström’s Macroglobulinemia (WM)

WM is a rare lymphoma representing approximately 1% of all non-Hodgkin lymphomas and typically progresses slowly after diagnosis.1 In Europe, the estimated incidence of WM is approximately 7 for every 1 million men and 4 for every 1 million women.2
About the Zanubrutinib Clinical Trial Program

Clinical trials of zanubrutinib include:

Fully-enrolled Phase 3 ASPEN clinical trial in patients with Waldenström’s macroglobulinemia (WM) comparing zanubrutinib to ibrutinib (NCT03053440), currently the only approved BTK inhibitor for WM;

Phase 3 SEQUOIA trial comparing zanubrutinib with bendamustine plus rituximab in patients with treatment-naive (TN) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) (NCT03336333);

Phase 3 ALPINE trial comparing zanubrutinib to ibrutinib in patients with relapsed/refractory (R/R) CLL/SLL (NCT03734016);

Phase 3 MANGROVE trial comparing zanubrutinib and rituximab to bendamustine and rituximab in patients with untreated mantle cell lymphoma (MCL) (NCT04002297);

Phase 2 MAGNOLIA trial in patients with R/R marginal zone lymphoma (MZL) (NCT03846427);

Phase 2 ROSEWOOD trial (NCT03332017) in China comparing obinutuzumab and zanubrutinib vs obinutuzumab alone in treating patients with R/R FL;

Phase 2 trial (NCT04382586) in the U.S. comparing zanubrutinib plus supportive care to placebo plus supportive care for the treatment of patients with COVID-19 disease and pulmonary distress;

Phase 2 trial (NCT04116437) in the U.S. in patients with previously treated B-cell lymphoma intolerant of prior treatment with ibrutinib and/or acalabrutinib;

Phase 2 trial (NCT03332173) in China in patients with R/R WM; and

Completed Phase 2 trials in China in patients with R/R MCL (NCT03206970) and R/R CLL/SLL (NCT03206918).
About BRUKINSA (zanubrutinib)

BRUKINSA is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK), discovered by BeiGene scientists, that is currently being evaluated globally in a broad pivotal clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies.
BRUKINSA was approved by the U.S. FDA to treat adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy on November 14, 2019. This indication was approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
BRUKINSA was approved in China for the treatment of MCL in adult patients who have received at least one prior therapy and CLL/SLL in adult patients who have received at least one prior therapy in June 2020.
BRUKINSA is not approved outside of the United States and China.

IMPORTANT U.S. SAFETY INFORMATION FOR BRUKINSA (ZANUBRUTINIB)

Warnings and Precautions Hemorrhage
Fatal and serious hemorrhagic events have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher bleeding events including intracranial and gastrointestinal hemorrhage, hematuria and hemothorax have been reported in 2% of patients treated with BRUKINSA monotherapy. Bleeding events of any grade, including purpura and petechiae, occurred in 50% of patients treated with BRUKINSA monotherapy.
Bleeding events have occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Co-administration of BRUKINSA with antiplatelet or anticoagulant medications may further increase the risk of hemorrhage.
Monitor for signs and symptoms of bleeding. Discontinue BRUKINSA if intracranial hemorrhage of any grade occurs. Consider the benefit-risk of withholding BRUKINSA for 3-7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.
Infections

Fatal and serious infections (including bacterial, viral, or fungal) and opportunistic infections have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher infections occurred in 23% of patients treated with BRUKINSA monotherapy. The most common Grade 3 or higher infection was pneumonia. Infections due to hepatitis B virus (HBV) reactivation have occurred.
Consider prophylaxis for herpes simplex virus, pneumocystis jiroveci pneumonia and other infections according to standard of care in patients who are at increased risk for infections. Monitor and evaluate patients for fever or other signs and symptoms of infection and treat appropriately.
Cytopenias

Grade 3 or 4 cytopenias, including neutropenia (27%), thrombocytopenia (10%), and anemia (8%) based on laboratory measurements, were reported in patients treated with BRUKINSA monotherapy.
Monitor complete blood counts during treatment and treat using growth factor or transfusions, as needed.

Second Primary Malignancies
Second primary malignancies, including non-skin carcinoma, have occurred in 9% of patients treated with BRUKINSA monotherapy. The most frequent second primary malignancy was skin cancer (basal cell carcinoma and squamous cell carcinoma of skin), reported in 6% of patients. Advise patients to use sun protection.
Cardiac Arrhythmias

Atrial fibrillation and atrial flutter have occurred in 2% of patients treated with BRUKINSA monotherapy. Patients with cardiac risk factors, hypertension, and acute infections may be at increased risk. Grade 3 or higher events were reported in 0.6% of patients treated with BRUKINSA monotherapy. Monitor signs and symptoms for atrial fibrillation and atrial flutter and manage as appropriate.
Embryo-Fetal Toxicity

Based on findings in animals, BRUKINSA can cause fetal harm when administered to a pregnant woman. Administration of zanubrutinib to pregnant rats during the period of organogenesis caused embryo-fetal toxicity, including malformations at exposures that were 5 times higher than those reported in patients at the recommended dose of 160 mg twice daily. Advise women to avoid becoming pregnant while taking BRUKINSA and for at least 1 week after the last dose. Advise men to avoid fathering a child during treatment and for at least 1 week after the last dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.
Adverse Reactions

The most common adverse reactions in > 10% of patients who received BRUKINSA were neutrophil count decreased (53%), platelet count decreased (39%), upper respiratory tract infection (38%), white blood cell count decreased (30%), hemoglobin decreased (29%), rash (25%), bruising (23%), diarrhea (20%), cough (20%), musculoskeletal pain (19%), pneumonia
(18%), urinary tract infection (13%), hematuria (12%), fatigue (11%), constipation (11%), and hemorrhage (10%). The most frequent serious adverse reactions were pneumonia (11%) and hemorrhage (5%).

Of the 118 patients with MCL treated with BRUKINSA, 8 (7%) patients discontinued treatment due to adverse reactions in the trials. The most frequent adverse reaction leading to treatment discontinuation was pneumonia (3.4%). One (0.8%) patient experienced an adverse reaction leading to dose reduction (hepatitis B).

Drug Interactions

CYP3A Inhibitors: When BRUKINSA is co-administered with a strong CYP3A inhibitor, reduce BRUKINSA dose to 80 mg once daily. For co-administration with a moderate CYP3A inhibitor, reduce BRUKINSA dose to 80 mg twice daily.
CYP3A Inducers: Avoid co-administration with moderate or strong CYP3A inducers.
Specific Populations

Hepatic Impairment: The recommended dose of BRUKINSA for patients with severe hepatic impairment is 80 mg orally twice daily.
INDICATION

BRUKINSA is a kinase inhibitor indicated for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.
This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

On June 18, 2020 Linnaeus Therapeutics, Inc. (Linnaeus), a privately held clinical-stage biopharmaceutical company focused on the development and commercialization of novel small-molecule oncology therapeutics, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for LNS8801 for the treatment of patients with metastatic or unresectable melanoma who have progressed on or after anti–programmed cell death receptor or ligand (anti–PD-1/L1) therapy (Press release, Linnaeus Therapeutics, JUN 18, 2020, View Source [SID1234561305]).

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Linnaeus is currently evaluating LNS8801 in a phase 1 clinical trial in patients with advanced cancer. The company expects to identify the recommended phase 2 dose this summer and to begin its phase 2 program evaluating LNS8801 as a monotherapy and in combination with targeted therapies in early fall.

LNS8801 is a first-in-class, orally bioavailable, small-molecule that is a highly specific and potent agonist of the G-protein estrogen receptor (GPER). GPER is widely expressed on cancers. Agonizing GPER both stops cancers from proliferating and makes them more visible to the immune system.

"Receiving Fast Track designation for LNS8801 is an important step in its clinical development as we near the end of our phase 1 dose-escalation study and advance LNS8801 into phase 2 clinical trials," said Patrick Mooney, MD, Chief Executive Officer of Linnaeus. "We are pleased that the FDA recognizes the potential of LNS8801 to help patients with melanoma who have progressed after anti–PD-1/L1 therapy."

About Fast Track Designation

Fast Track designation is a process designed to facilitate the expedited development and review of new drugs that treat serious or life-threatening conditions and that have demonstrated the potential to fill an unmet medical need. The purpose is to advance new drugs earlier for patients who need them.

A company with a drug that receives Fast Track designation is eligible for some or all of the following:

More frequent meetings with the FDA to discuss the drug’s development and ensure collection of the appropriate data needed to support drug approval
More frequent written communication from the FDA about such things as the design of the proposed clinical trials and use of biomarkers
Eligibility for Accelerated Approval and Priority Review if relevant criteria are met
Rolling Review, which means that a drug company can submit completed sections of its New Drug Application (NDA) for review by the FDA, rather than waiting until every section of the NDA is completed before the entire application can be reviewed. NDA review usually does not begin until the drug company has submitted the entire application to the FDA.
About LNS8801

LNS8801 is an orally bioavailable and highly specific agonist of GPER whose activity is dependent on the expression of GPER. GPER activation suppresses well-known tumor-associated genes, such as c-Myc and PD-L1. In preclinical cancer models, LNS8801 displays potent antitumor activities across a wide range of tumor types, rapidly shrinking tumors and inducing immune memory. LNS8801 monotherapy has shown significant antitumor activity, including inducing complete responses that are immune to rechallenge. LNS8801 also has shown effects when combined with targeted therapies, chemotherapies, and immunotherapies. LNS8801 is currently in a phase 1/2 clinical trial in patients with advanced cancer at six comprehensive cancer centers in the United States.