On March 30, 2021 Exelixis, Inc. (Nasdaq: EXEL) reported that COSMIC-313, the phase 3 pivotal trial evaluating the combination of cabozantinib (CABOMETYX), nivolumab (OPDIVO) and ipilimumab (YERVOY) versus the combination of nivolumab and ipilimumab in patients with previously untreated advanced intermediate- or poor-risk renal cell carcinoma (RCC), has completed enrollment (Press release, Exelixis, MAR 30, 2021, https://ir.exelixis.com/news-releases/news-release-details/exelixis-announces-enrollment-completion-phase-3-cosmic-313 [SID1234577369]). The primary endpoint of the trial is progression-free survival, and additional endpoints include overall survival and objective response rate.

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!

"Following the promising final results of a phase 1b trial evaluating this triplet combination in advanced genitourinary tumors, this milestone in the phase 3 pivotal trial brings us a step closer to understanding whether cabozantinib in combination with nivolumab and ipilimumab may improve outcomes for patients with previously untreated advanced kidney cancer," said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. "We look forward to sharing initial results from the event-driven analysis of COSMIC-313 when available and to learning more about the potential of cabozantinib in combination with immunotherapies."

COSMIC-313 is a multicenter, randomized, double-blind, controlled phase 3 pivotal trial that enrolled approximately 840 patients at 180 sites globally. Patients were randomized 1:1 to receive cabozantinib plus nivolumab and ipilimumab or matching placebo plus nivolumab and ipilimumab. The design of COSMIC-313 was informed by the results of the CheckMate -214 trial that supported regulatory approval of nivolumab in combination with ipilimumab for the first-line treatment of patients with intermediate- and poor-risk RCC, and by results from the phase 1b study of cabozantinib in combination with nivolumab with or without ipilimumab in patients with relapsed or refractory metastatic genitourinary cancers, including RCC. Final results from that phase 1b trial were presented during the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s Genitourinary Cancers Symposium.

Bristol Myers Squibb is providing nivolumab and ipilimumab for use in this trial.

More information about this trial is available at ClinicalTrials.gov.

About RCC
The American Cancer Society’s 2021 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.1 Clear cell RCC is the most common form of kidney cancer in adults.2 If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 13%.1 Approximately 32,000 patients in the U.S. and 71,000 worldwide will require systemic treatment for advanced kidney cancer in 2021.3

About 70% of RCC cases are known as "clear cell" carcinomas, based on histology.4 The majority of clear cell RCC tumors have below-normal levels of a protein called von Hippel-Lindau, which leads to higher levels of MET, AXL and VEGF.5,6 These proteins promote tumor angiogenesis (blood vessel growth), growth, invasiveness and metastasis.7,8,9,10 MET and AXL may provide escape pathways that drive resistance to VEGF receptor inhibitors.6,7

About CABOMETYX (cabozantinib)
In the U.S., CABOMETYX tablets are approved for the treatment of patients with advanced RCC; for the treatment of patients with hepatocellular carcinoma who have been previously treated with sorafenib; and for patients with advanced RCC as a first-line treatment in combination with OPDIVO. CABOMETYX tablets have also received regulatory approvals in the European Union and additional countries and regions worldwide. In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the United States and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the United States.

CABOMETYX is not indicated for use in combination with nivolumab and ipilimumab in previously untreated advanced renal cell carcinoma.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS
Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients in RCC and HCC studies. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage. Do not administer CABOMETYX to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

Perforations and Fistulas: Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. Gastrointestinal (GI) perforations, including fatal cases, occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms of fistulas and perforations, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a Grade 4 fistula or a GI perforation.

Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX patients. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic events that require medical intervention.

Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension was reported in 36% (17% Grade 3 and <1% Grade 4) of CABOMETYX patients. Do not initiate CABOMETYX in patients with uncontrolled hypertension. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis.

Diarrhea: Diarrhea occurred in 63% of CABOMETYX patients. Grade 3 diarrhea occurred in 11% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 diarrhea, Grade 3 diarrhea that cannot be managed with standard antidiarrheal treatments, or Grade 4 diarrhea.

Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in 44% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.

Hepatotoxicity: CABOMETYX in combination with nivolumab can cause hepatic toxicity with higher frequencies of Grades 3 and 4 ALT and AST elevations compared to CABOMETYX alone.

Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes than when the drugs are administered as single agents. For elevated liver enzymes, interrupt CABOMETYX and nivolumab and consider administering corticosteroids.

With the combination of CABOMETYX and nivolumab, Grades 3 and 4 increased ALT or AST were seen in 11% of patients. ALT or AST >3 times ULN (Grade ≥2) was reported in 83 patients, of whom 23 (28%) received systemic corticosteroids; ALT or AST resolved to Grades 0-1 in 74 (89%). Among the 44 patients with Grade ≥2 increased ALT or AST who were rechallenged with either CABOMETYX (n=9) or nivolumab (n=11) as a single agent or with both (n=24), recurrence of Grade ≥2 increased ALT or AST was observed in 2 patients receiving CABOMETYX, 2 patients receiving nivolumab, and 7 patients receiving both CABOMETYX and nivolumab.

Adrenal Insufficiency: CABOMETYX in combination with nivolumab can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold CABOMETYX and/or nivolumab depending on severity.

Adrenal insufficiency occurred in 4.7% (15/320) of patients with RCC who received CABOMETYX with nivolumab, including Grade 3 (2.2%), and Grade 2 (1.9%) adverse reactions. Adrenal insufficiency led to permanent discontinuation of CABOMETYX and nivolumab in 0.9% and withholding of CABOMETYX and nivolumab in 2.8% of patients with RCC.

Approximately 80% (12/15) of patients with adrenal insufficiency received hormone replacement therapy, including systemic corticosteroids. Adrenal insufficiency resolved in 27% (n=4) of the 15 patients. Of the 9 patients in whom CABOMETYX with nivolumab was withheld for adrenal insufficiency, 6 reinstated treatment after symptom improvement; of these, all (n=6) received hormone replacement therapy and 2 had recurrence of adrenal insufficiency.

Proteinuria: Proteinuria was observed in 7% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. Discontinue CABOMETYX in patients who develop nephrotic syndrome.

Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1% of CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain, or slow healing of the mouth or jaw after dental surgery. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures, if possible. Withhold CABOMETYX for development of ONJ until complete resolution.

Impaired Wound Healing: Wound complications occurred with CABOMETYX. Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer CABOMETYX for at least 2 weeks after major surgery and until adequate wound healing is observed. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic findings on MRI, can occur with CABOMETYX. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.

Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to initiating CABOMETYX and advise them to use effective contraception during treatment and for 4 months after the last dose.

ADVERSE REACTIONS

The most common (≥20%) adverse reactions are:

CABOMETYX as a single agent: diarrhea, fatigue, decreased appetite, PPE, nausea, hypertension, vomiting, weight decreased, constipation, and dysphonia.

CABOMETYX in combination with nivolumab: diarrhea, fatigue, hepatotoxicity, PPE, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.

DRUG INTERACTIONS

Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice.

Strong CYP3A4 Inducers: If coadministration with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John’s wort.

USE IN SPECIFIC POPULATIONS

Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose.

Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. Avoid CABOMETYX in patients with severe hepatic impairment.

On March 30, 2021 Forma Therapeutics Holdings, Inc. (Nasdaq: FMTX), a clinical-stage biopharmaceutical company focused on rare hematologic diseases and cancers, reported financial results for the fourth quarter and full year ended December 31, 2020 (Press release, Forma Therapeutics, MAR 30, 2021, View Source [SID1234577368]). The company also highlighted recent progress and upcoming milestones for its pipeline programs.

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!

"2020 was a very productive year for Forma, starting with our initial public offering in June and including positive clinical data and progress on our key development programs targeting sickle cell disease, AML and glioma, as well as prostate cancer," said Frank Lee, president and chief executive officer of Forma. "With important events in 2021 for our compounds in development, we look forward to furthering our mission to bring breakthrough therapies to people living with rare hematologic diseases and cancers."

Key Business and Clinical Highlights

PKR Program in Sickle Cell Disease (SCD):

Positive Phase 1 results of FT-4202 presented at scientific conferences. At the European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress in June 2020, results from a single ascending dose trial demonstrated a favorable tolerability profile and pharmacokinetic/pharmacodynamic (PK/PD) effects in patients with SCD who were administered a 700mg dose of FT-4202. Subsequently, at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in December 2020, data were presented from the ongoing randomized, placebo-controlled Phase 1 multiple ascending dose (MAD) trial. Results from the 300mg MAD1 dose cohort following 14 days of treatment showed an increase in hemoglobin of 1g/dL or greater in 6 of 7 (86%) patients vs. 0% of patients receiving placebo. In addition, markers of hemolysis such as indirect bilirubin, reticulocytes and lactate dehydrogenasewere improved, and measures of oxygen affinity and deformability suggested improvement in RBC health. FT-4202 was generally well-tolerated with no serious adverse events attributed to treatment with the compound.
Positive FT-4202 600 mg multiple ascending dose cohort data support doses being evaluated in Phase 2/3 registrational trial, called the Hibiscus Study. Doubling the dose of FT-4202 to 600 mg daily for 14 days compared to the previous 300 mg cohort was well-tolerated with no dose-limiting toxicities or treatment-related adverse events observed. Improvements in hematologic (hemoglobin and reticulocytes) and hemolytic (bilirubin and LDH) parameters were comparable to that observed with 300 mg dose, with best response typically at the end of the 14-day treatment period. Across 300 mg and 600 mg cohorts, 10 of 14 (71%) patients on FT-4202 for 14 days achieved a hemoglobin increase ≥ 1 g/dL from baseline. The phase 2/3 Hibiscus Study is currently enrolling people living with sickle cell disease (SCD). This adaptive, randomized, placebo-controlled, double-blind, multi-center trial is expected to enroll approximately 344 adults and adolescents with SCD. FT-4202 doses of 200mg and 400mg administered once-daily are being evaluated in the Phase 2 portion of the trial. Primary endpoints in the Phase 3 portion of the trial are hemoglobin response rate at week 24 (increase of > 1 g/dL from baseline), and annualized vaso-occlusive crisis rate during the 52-week blinded treatment period.
CPB/p300 Program in Prostate Cancer:

Preclinical data presented at scientific conference. At the American Association for Cancer Research (AACR) (Free AACR Whitepaper) virtual meeting in June 2020, a poster was presented with preclinical data for FT-6876, a potent and selective inhibitor of CBP/p300, a known co-activator of the androgen receptor (AR) and a driver of metastatic castration-resistant prostate cancer (mCRPC). The data demonstrated antitumor activity of FT-6876 in AR-dependent breast cancer cell lines and highlight the possible role of CBP/p300 in proliferation and survival of AR-dependent tumors, such as prostate cancer. FT-6876 is a research compound related to FT-7051, although with differing PK/PD properties.
FT-7051 Phase 1 clinical trial initiated for the treatment of metastatic castration-resistant prostate cancer (mCRPC). In January 2021, Forma announced that the first patient was dosed in the ongoing Phase 1 trial. The trial is a multicenter, open-label evaluation of the safety and tolerability, preliminary anti-tumor activity (PSA and radiographic responses), and PK/PD of FT-7051 in men with mCRPC who have progressed despite prior therapy with at least one anti-androgen therapy. The trial will include genetic mutation analysis to identify tumors with AR-v7 splice variants, against which there are no approved therapies. This is an adaptive trial design, intended to accelerate the escalation to potentially therapeutic doses and yield important safety information, as well as the identification of biomarkers of clinical benefit such as prostate specific antigen (PSA).
IDH1 Program in AML and Glioma:

Announced positive registrational data for olutasidenib in relapsed/refractory acute myeloid leukemia (R/R AML). In October 2020, Forma announced positive results from the planned interim analysis (IA2) of the Phase 2 registration trial in R/R AML patients with isocitrate dehydrogenase 1 gene mutations (IDH1m). Olutasidenib demonstrated favorable tolerability as a monotherapy and achieved the primary endpoint of a composite complete remission (CR+CRh, or complete remission plus complete remission with partial hematologic recovery) rate of 33.3% (30% CR and 3% CRh). While a median duration of CR/CRh has not been reached, a sensitivity analysis (with a hematopoietic stem cell transplant as the end of a response) indicated a median duration of CR/CRh to be 13.8 months. Safety results were consistent with previously reported Phase 1 clinical trial results. Additional data and analyses indicate that the overall response rate (ORR), comprised CR, CRh, CRi, partial response (PR), and morphologic leukemia-free state (MLFS), was 46% and the median duration of ORR was 11.7 months. The median overall survival (OS) was 10.5 months. For patients with CR/CRh, the median OS has not yet been reached, but the estimated 18-month survival is 87%. The most frequently reported treatment emergent adverse events (≥20%) were nausea (38%), constipation (25%), increased white blood cell count (25%), decreased RBC count (24%), pyrexia (23%), febrile neutropenia (22%), and fatigue (21%). Grade 3/4 adverse events occurring in greater than 10% of patients, regardless of causality, were febrile neutropenia (20%), decreased RBC count (19%), decreased platelet count (16%), and decreased neutrophil count (13%).
An exploratory Phase 1 trial of olutasidenib for glioma showed evidence of disease control. Data presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) meeting in June 2020 demonstrated the brain penetrant properties of olutasidenib and preliminary clinical activity, which suggest potential for response and prolonged disease control in the enhanced (grade III/IV) R/R IDH1-mutated glioma. Among 24 evaluable patients treated (4 grade II, 13 grade III, 7 grade IV), one patient had a partial response and 11 patients had stable disease, as determined by investigator response assessment in neuro-oncology, or RANO, criteria. Twenty-two of the patients’ responses were also evaluated by volumetric changes at a central review, where four patients had more than 50% tumor reduction, one patient had 25% to 50% tumor reduction, and an additional seven patients had prolonged stable disease.
Corporate Achievements:

Successful initial public offering in June 2020 and follow-on equity offering in December 2020. On June 23, 2020, the Company completed an initial public offering (IPO) in which the Company issued and sold 15,964,704 shares of its common stock at a public offering price of $20.00 per share. The Company raised approximately $293.3 million in net proceeds after deducting underwriting discounts and commissions and offering expenses. On December 15, 2020, the Company completed an underwritten public offering of 6,095,000 shares of its common stock at a public offering price of $45.25 per share. The Company raised approximately $258.6 million in net proceeds after deducting underwriting discounts and commissions and offering expenses.
Three new board of directors appointments. In July 2020, Wayne A. I. Frederick, M.D., was elected to serve on Forma’s board of directors. Dr. Frederick is the President of Howard University, as well as the Charles R. Drew Professor in Surgery at Howard University’s College of Medicine, and a distinguished researcher and practicing surgeon.

In September 2020, Forma announced the appointment of industry veteran Thomas G. Wiggans to its board of directors. Mr. Wiggans has led successful biopharmaceutical companies from start-up stage into the clinic and later global commercialization and served on the boards of numerous public and private companies.

In January 2021, Forma announced the appointment of Selwyn M. Vickers, M.D., to its board of directors. Dr. Vickers is a world-renowned surgeon, pancreatic cancer researcher and pioneer in health disparities research. He currently serves as senior vice president of medicine and dean of the School of Medicine at The University of Alabama at Birmingham (UAB).
Upcoming Milestones

Phase 1 FT-4202 randomized cohorts successfully completed; open label extension ongoing. Patients with sickle cell disease are now directly enrolling into the 12-week open label extension (OLE) with the 400mg daily dose, which was previously limited to patients who completed the 600mg dose cohort. Initial results from the ongoing 400mg 12-week open label extension are anticipated to be announced at a scientific congress in the second quarter of 2021, and full results expected at a scientific congress in late 2021.
Initial Phase 1 clinical results from FT-7051 in mCRPC anticipated later this year. This adaptive trial is designed to assess multiple doses of FT-7051 with dose escalation dependent upon safety and tolerability. Initial results are anticipated in the second half of 2021, which may include safety/tolerability, PK/PD results and preliminary biomarker data.
NDA being prepared for olutasidenib in R/R AML. Forma is preparing a new drug application (NDA) for submission to the U.S. Food and Drug Administration for refractory/relapsing AML patients with an IDH1 mutation. In addition, a manuscript is being prepared for publication of Phase 1 glioma results.
Possibility of COVID-19 impact remains. The COVID-19 pandemic remains a factor in the successful completion of these milestones. Many clinical trials across the biopharma industry have been impacted by the COVID-19 pandemic, with clinical trial sites implementing new policies in response to COVID-19, resulting in potential delays to enrollment of clinical trials or changes in the ability to access sites participating in clinical trials.
Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $645.6 million as of December 31, 2020, as compared to $173.2 million as of December 31, 2019. Current cash runway is projected through the third quarter of 2024.
Research and Development (R&D) Expenses: R&D expenses were $24.9 million and $93.4 million for the quarter and year ended December 31, 2020, compared to $27.0 million and $111.3 million for the quarter and year ended December 31, 2019. The decline was attributable to a decrease in spending on internal research and development primarily due to restructuring in January 2019, and reductions in spending on olutasidenib and FT-8225, which were partially offset by increases in FT-4202 expenses to conduct the Phase 1 trial, clinical product manufacturing, and preparations for the pivotal Phase 2/3 trial.
General and Administrative (G&A) Expenses: G&A expenses were $7.9 million and $30.8 million for the quarter and year ended December 31, 2020, compared to $6.8 million and $24.4 million for the quarter and year ended December 31, 2019. The increase in general and administrative expense was primarily attributable to a $3.2 million increase in stock compensation expense; $1.2 million increase in insurance related expenses; $1.2 million increase in professional fees; $0.5 million increase in personnel-related costs due to executive and staff hiring, recruiting and an increase in facilities; and IT related expenses of $0.2 million.
Net Income/Loss: Net loss was $28.6 million and $70.4 million for the quarter and year ended December 31, 2020, compared to $24.7 million and $34.8 million for the quarter and year ended December 31, 2019.
Forma will conduct a conference call and webcast on March 30th at 8 a.m. Eastern Standard Time (EST) to discuss 2020 year-end financial results and business update. The call can be accessed by dialing (833) 301-1146 in the U.S., and (914) 987-7386 internationally, with conference ID 5893542.

The live webcast will be available in the "News & Investors" section of Forma’s website www.formatherapeutics.com.

On March 30, 2021 Ascendis Pharma A/S (Nasdaq: ASND), a biopharmaceutical company that utilizes its innovative TransCon technologies to create product candidates that address unmet medical needs, reported that the company will participate at the J.P. Morgan 10th Annual Napa Valley Biotech Forum (Press release, Ascendis Pharma, MAR 30, 2021, View Source [SID1234577367]). Company executives will provide a business overview and an update on the Company’s pipeline programs.

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!

Details

Event J.P. Morgan 10th Annual Napa Valley Biotech Forum
Location Virtual
Date Tuesday, March 30, 2021
Time 4:00 p.m. Eastern Time
A live audio webcast of the presentation will be available on the Investors and News section of the Company’s website at www.ascendispharma.com. A webcast replay will also be available on the Company’s website shortly after conclusion of the event for 30 days.

On March 30, 2021 Bicycle Therapeutics plc (NASDAQ: BCYC), a biotechnology company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported progress updates for its Bicycle-based partnered programs outside of oncology (Press release, Bicycle Therapeutics, MAR 30, 2021, View Source [SID1234577366]).

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!

"Over the last five years, Bicycle’s strategy has been to use our novel technology to discover and develop a pipeline of innovative assets in oncology while additionally using non-dilutive funding and collaborations to explore the therapeutic potential of Bicycles in disease areas outside of oncology. Today, for the first time, we are providing an overview on our progress in demonstrating the broad utility of this platform to create molecules with the potential to treat some of the most serious diseases and address future healthcare challenges," said Kevin Lee, Ph.D., Chief Executive Officer of Bicycle Therapeutics. "It’s incredibly exciting to see how the Company has worked innovatively and highly collaboratively with many diverse institutions to address these challenges and, at the same time, generated significant revenues to offset the costs of developing and progressing our internal oncology pipeline. I would like to thank all of our collaborators for their enthusiasm in this endeavor and look forward to continuing our work to advance these important molecules."

Bicycle has achieved the first milestone in its collaboration with Dementia Discovery Fund (DDF) and the University of Oxford’s ARUK Oxford Drug Discovery Institute (ODDI)

The Company identified and optimized nM affinity Bicycles to TREM2, a genetically validated target for the treatment of dementia, and nM affinity Bicycles to transferrin receptor 1 (TfR1), a molecular shuttle. In 2019, Bicycle established a collaboration with DDF, later expanded to include ODDI, to use Bicycle technology for the discovery and development of potential novel therapeutics for the treatment of dementia. The three parties are collaborating to identify and characterize Bicycles that bind to and activate TREM2, a genetically validated dementia target. As part of the collaboration, Bicycle is also using its technology to identify binders to TfR1, a blood brain barrier transporter, that could potentially enable delivery of Bicycles, or any other molecular payload, into the central nervous system (CNS), or other organ systems, expressing TfR1. Under the terms of the collaboration with DDF, Bicycle retains all rights to the TfR1 molecules outside of the license granted for use with targets defined within the DDF collaboration.
Bicycle advances platform in multiple anti-infective areas, including antimicrobials and antivirals

Innovate UK’s Biomedical Catalyst (BMC) awarded the Company funding to advance a Bicycle inhibitor for a key cell wall biosynthesis target in Enterobacterales, Penicillin Binding Protein 3 (PBP3). Bicycle is using its proprietary platform to try to address the significant healthcare challenge of antimicrobial resistance and has identified several potential Bicycle PBP3 inhibitors. Through grants awarded by the UK government and in collaboration with investigators at the University of Warwick, Bicycle intends to progress these PBP3 inhibitors, potentially representing the first novel class of antibiotics identified in decades, to candidate and initial toxicology testing.
Innovate UK, under a specific program targeting key technologies to rapidly respond to the challenge of COVID-19 (UKRI Ideas to Address COVID-19 – Innovate UK Article 25), provided funding to support Bicycle’s efforts to discover new healthcare solutions to the SARS-CoV-2 pandemic. Bicycle has identified numerous discrete families of Bicycles which bind to at least 10 different epitopes on the SARS-CoV-2 spike protein, binders to the Nucleocapsid protein and the viral attachment site on the host ACE2 human receptor. Through Bicycle’s partnership with researchers at the MRC Laboratory of Molecular Biology, Bicycles identified by these screens have demonstrated nanomolar activity in inhibiting SARS-CoV-2 infection of human lung cells. These monomeric Bicycles have been conjugated together to make a diverse range of bi-paratopic and multi-valent small molecules (less than 10kD), some of which are active in the picomolar range in viral entry assays and may be resistant to the current SARS-CoV-2 variants of concern. Bicycle continues to advance these novel compounds in pre-clinical evaluation. Bicycle has also formed partnerships with diagnostic experts to evaluate its novel SARS-CoV-2 binding Bicycles in Lateral Flow Tests and other diagnostic screening formats.
Bicycle has made significant progress through partnerships with biopharmaceutical therapeutic area leaders in indications outside of oncology

The Company has successfully discovered and advanced targets outside of oncology through the ongoing collaboration with AstraZeneca, a global biopharmaceutical company, to discover novel agents for the treatment of respiratory and cardiometabolic diseases. Two assets have been transitioned to AstraZeneca for further development and are currently being progressed in their discovery pipeline. Two additional assets achieved transition criteria and were transitioned to AstraZeneca but were returned to Bicycle by AstraZeneca.
Bicycle has also identified targets in its collaboration with Bioverativ (acquired by Sanofi in 2018) for the treatment of rare hematological diseases. The Bioverativ collaboration successfully identified nM multi-valent inhibitors to P-Selectin, which inhibited human neutrophil binding and rolling, with potential applications in sickle cell disease and other inflammatory diseases. The Bioverativ collaboration also identified the first small molecule Factor VIII mimetic for the potential treatment of Hemophilia A. This mimetic is comprised of a multivalent Bicycle binding to both Factor IX and Factor X, leading to the production of activated Factor X (FXa), which successfully activated thrombin in plasma from Hemophilia A patients ex vivo. In 2019, Sanofi elected not to pursue further development, and the collaboration agreement was terminated. These "lead stage" assets have now been returned to Bicycle.
Kevin Lee commented, "With four Bicycle molecules now in clinical trials for both oncology and non-oncology indications, the technology has shown initial evidence of clinical tolerability and suitability for pharmaceutical development, and I look forward to seeing how Bicycles may bring important new treatment opportunities to poorly served patients in additional therapeutic areas."

On March 30, 2021 VBL Therapeutics (Nasdaq: VBLT) reported that it will host a virtual R&D Day for analysts and investors beginning at 10:00am ET on Tuesday, April 6, 2021 (Press release, VBL Therapeutics, MAR 30, 2021, View Source [SID1234577365]). The event will include presentations from Professor Dror Harats, M.D, Chief Executive Officer, Dr. Bradley Monk, M.D., FACS, FACOG, Chair of the OVAL Study Steering Committee, and Dr. Tami Rachmilewitz, M.D, Vice President of Clinical Development, and will focus on the Company’s clinical-stage pipeline including lead program, VB-111. The live event can be accessed at View Source

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!

Following the event, an archive will be available via the "Events and Presentations" section of the VBL investor relations website at View Source