On May 10, 2022 GeneCentric Therapeutics, a company making precision medicine more precise through RNA-based diagnostics, reported an upcoming presentation of initial results from the GARNER (Genomic Analysis of high-Risk Non-muscle invasive bladder cancer) real-world study at the 2022 American Urological Association (AUA) Annual Meeting, which is being held in New Orleans, Louisiana, May 13-16, 2022 (Press release, GeneCentric Therapeutics, MAY 10, 2022, View Source [SID1234614066]). In this moderated poster presentation, the frequency of fibroblast growth factor receptor (FGFR) alterations in high-risk non-muscle invasive bladder cancer (HR-NMIBC) and the association with bacillus Calmette-Guérin (BCG) outcome will be discussed.

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The GARNER Study is the largest HR-NMIBC real-world patient cohort ever assembled with both clinical and genomic detail and the first study of the broader GARNER Bladder Cancer Program. The study is a collaboration between the Department of Urology at Erasmus MC Cancer Institute (EMC), Janssen Research & Development, LLC (Janssen) and GeneCentric Therapeutics. The collaboration, led at EMC by Tahlita Zuiverloon, MD, PhD, Principal Investigator at the Erasmus MC Urothelial Cancer Research Group (EUCRG), involves retrospective longitudinal, genomic analysis of samples from a cohort of almost 600 NMIBC patients who underwent surgery and adjuvant BCG treatment.

"The initial results from the GARNER Study provide a comprehensive picture of FGFR alteration frequency and other findings and provides a deeper understanding of drivers of disease progression, as well as potential factors related to treatment response and failure or drug resistance," said Dr Zuiverloon. "We look forward to presenting the initial findings from the study with our collaborators at GeneCentric and Janssen as we continue to explore the complexities of FGFR in HR-NMIBC."

While topline clinicogenomic results from this study will be presented at AUA2022, further results will be presented as part of a subsequent publication.

Details regarding the presentation are provided below and will be available following the meeting at View Source

Title: Frequency of Fibroblast Growth Factor Receptor Alterations and Association with Bacillus Calmette-Guérin Outcomes in a Real-World Genomic Analysis of High-Risk Non-Muscle-Invasive Bladder Cancer (GARNER) Study

First Author: Tahlita C.M. Zuiverloon, MD, Department of Urology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands

On May 10, 2022 Celsion Corporation (NASDAQ: CLSN), a clinical-stage company focused on DNA-based immunotherapy and next-generation vaccines, reported an update on the progress made in the Company’s two lead development programs (Press release, Celsion, MAY 10, 2022, View Source [SID1234614059]).

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"We continue to make important progress in both of our lead development programs, and I am very pleased by the encouraging results to date," said Michael H. Tardugno, chairman, president and chief executive officer of Celsion. "Our PLACCINE DNA-based vaccine platform was recently highlighted at the 2022 World Vaccine Congress and is demonstrating its potential for rapid design and capability for targeting two or more different COVID variants in one vaccine. We have demonstrated a proof-of-concept utilizing a standard mouse model showing that PLACCINE can target two variants and produce robust levels of IgG, neutralizing antibodies, and t-cell responses. This proof-of-concept data is comparing favorably to commercial vaccines in mouse models with this data recently reported at the World Vaccine Congress. A vaccine that targets multiple strains at once and designed to provide long lasting immunity, is important in a future COVID-19 vaccination strategy. We are moving this program forward quickly and anticipate confirming our proof-of-concept in non-human primates over the next several months, with durability results later this year."

Mr. Tardugno continued, "OVATION 2, the Phase II study of our GEN-1 immunotherapy in ovarian cancer is 85% enrolled. In spite of all of the challenges presented by COVID 19, we are hopeful to complete enrollment in the third quarter of this year. Preclinical and clinical data gives us every reason to believe in GEN-1’s promise for ovarian cancer patients along with the support from leading medical researchers of the Gynecological Oncology Group (GOG). The GOG’s interest in forging a partnership to develop GEN-1 in ovarian cancer will assist Celsion in its plans for an accelerated registrational program. Meanwhile, FDA has approved our protocol for a second Phase II clinical trial to evaluate GEN-1 in combination with Avastin (bevacizumab) in patients with advanced ovarian cancer. Our preclinical tumor inhibition data provides a convincing basis for this study. We look forward to initiating this study at major comprehensive cancer hospitals later this year."

About PLACCINE

PLACCINE is a first in class DNA vaccine platform that can target multiple antigens and be administered with a standard intramuscular injection. PLACCINE was derived from the Company’s proprietary TheraPlas platform.

About GEN-1

GEN-1, an IL-12 DNA plasmid vector formulated into nanoparticles with a lipopolymeric delivery system, is the first product designed via the TheraPlas platform technology. GEN-1 may prove to be a safe and effective immunotherapy for treating various types of tumors by producing high levels of interleukin-12 (IL-12) at the site of tumors. IL-12 is one of the most active cytokines for stimulating an immune response against cancer. However, when administered as a recombinant protein requiring systemic administration, the pharmacokinetics of IL-12 requires that it be given by frequent, large bolus injections, resulting in serious toxicities that limit its use. GEN-1 addresses the toxicity issues associated with systemic IL-12. GEN-1’s nanoparticle design enables local administration (into the abdominal cavity) and cell transfection followed by persistent, local secretion of IL-12 at therapeutic levels, while avoiding the toxicities associated with recombinant IL-12.

On May 10, 2022 Prelude Therapeutics Incorporated ("Prelude") (Nasdaq: PRLD), a clinical-stage precision oncology company, reported financial results for the first quarter ended March 31, 2022, and provided an update on recent clinical and development pipeline progress (Press release, Prelude Therapeutics, MAY 10, 2022, View Source [SID1234614058]).

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"Prelude continues to make great progress in discovering and advancing a diverse pipeline of differentiated small molecules, and with our current cash runway, we have the opportunity to deliver on numerous meaningful milestones. I’m delighted to have Jane onboard and am confident in her leadership to guide focused clinical development of our pipeline and organizational growth," said Kris Vaddi, Ph.D., Chief Executive Officer.

"I’m excited to be a part of Prelude’s continued progress," said Jane Huang, M.D., President and Chief Medical Officer. "Looking ahead, we remain on track with ongoing development of our PRMT5 program, that will drive strategic decisions in the second half of the year. In parallel, we are focused on rapidly progressing our MCL1 candidate, PRT1419, into expansion and combination cohorts, and identifying a Phase 2 dose for PRT2527, our CDK9 inhibitor. We are also on track for Investigational New Drug (IND) submissions for both our SMARCA2 degrader and PRT3645, our brain penetrant CDK4/6 inhibitor, in the second half of the year. It’s clear that Prelude’s discovery engine, depth and breadth of the pipeline, coupled with an experienced management team, will position us to deliver potential medicines for patients with underserved cancers."

Recent Highlights and Upcoming Objectives

2022 AACR (Free AACR Whitepaper) Annual Meeting: During the quarter, Prelude participated in the 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. Four posters and one oral presentation providing data on Prelude’s clinical and preclinical pipeline molecules, with highly potent, selective and differentiated properties, were presented as part of the scientific conference.

PRMT5 Inhibitor Program: As previously announced, Prelude has prioritized PRT811 for clinical development in select expansion cohorts. Prelude intends to complete the data analyses of the ongoing expansion cohorts and expects to announce next steps for the PRMT5 program in 2H2022.

MCL1 Inhibitor Program: As previously announced, Prelude has prioritized development of the intravenous formulation of PRT1419, which demonstrated a desirable pharmacokinetic, pharmacodynamic and safety profile, with potential for differentiation from competitor compounds. Prelude remains on track to begin evaluating combinations with PRT1419 by mid-year.

CDK9 Inhibitor Program: Prelude remains on track to complete enrollment in the Phase 1 dose escalation study of PRT2527 and identify a recommended Phase 2 dose by 2H2022.

CDK4/6 Inhibitor Program: Prelude continues to expect to file an IND application mid-year, with the initiation of a Phase 1 trial of PRT3645 to follow in 2H2022.

SMARCA2/BRM Protein Degrader Program: Prelude remains on track to complete IND-enabling studies and submit an IND application by year-end 2022.
Corporate Update

In March 2022, Prelude announced the appointment of Jane Huang, M.D., effective April 4, 2022, to the newly created position of President and Chief Medical Officer. Dr. Huang joins Prelude from BeiGene Ltd., where she served as Chief Medical Officer, Hematology. Currently, Dr. Huang serves as an Adjunct Clinical Assistant Professor in Thoracic Oncology at Stanford University.
First Quarter 2022 Financial Results

Cash, Cash Equivalents and Marketable Securities: Cash, cash equivalents, and marketable securities as of March 31, 2022, were $266.2 million. Prelude anticipates that its existing cash, cash equivalents and marketable securities will fund Prelude’s operations into the second half of 2024.

Research and Development (R&D) Expenses: For the first quarter of 2022, R&D expense increased to $22.8 million from $16.5 million for the prior year period. Included in research and development expenses for the quarter ended March 31, 2022, was $3.2 million of non-cash expense related to stock-based compensation expense, including employee stock options, as compared to $1.8 million for the prior year period. The increase in research and development expense was primarily due to an increase in discovery-stage program expenses and from the growth and advancement of our clinical pipeline. We expect our research and development expenses to vary from quarter to quarter, primarily due to the timing of our clinical development activities.

General and Administrative (G&A) Expenses: For the first quarter of 2022, G&A expense increased to $7.5 million from $5.5 million for the prior year period. Included in the G&A expenses for the quarter ended March 31, 2022, was $3.6 million of non-cash expense related to stock-based compensation expense, including employee stock options, as compared to $2.0 million for the prior year period. The increase in G&A expense was primarily due to an increase in our non-cash stock compensation expense along with professional fees as we expanded our operations to support our research and development efforts.

Net Loss: For the three months ended March 31, 2022, net loss was $29.5 million, or $0.63 per share of common stock, basic and diluted compared to $21.3 million, or $0.47 per share, respectively, for the prior year period. Included in the net loss for the quarter ended March 31, 2022, was $6.8 million of non-cash expense related to the impact of expensing share-based payments, including employee stock options, as compared to $3.9 million for the prior year period.

On May 10, 2022 Biohaven Pharmaceutical Holding Company Ltd. (NYSE: BHVN), a biopharmaceutical company with a portfolio of innovative, late-stage product candidates targeting neurological diseases, including rare disorders, reported financial results for the first quarter ended March 31, 2022, and provided a review of recent accomplishments during and anticipated upcoming milestones (Press release, Biohaven Pharmaceutical, MAY 10, 2022, View Source [SID1234614057]).

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Vlad Coric, M.D., Chairman and Chief Executive Officer of Biohaven, commented, "NURTEC ODT continues to be the leading migraine therapy in the oral CGRP class and demonstrated 8% sequential TRx growth compared to the previous quarter. The approval of the prevention indication last year has established NURTEC ODT as the only "all-in-one" migraine therapy and contributed to the substantial year-over-year first quarter revenue growth of 182%. Although strong growth in the mix of 2-pack (16-tablet count) sales help to drive additional volume growth and increases the net price per prescription, seasonal resetting of commercial insurance plan annual deductibles largely explains the expected pressure observed on first quarter net revenue generation compared to the fourth quarter. Growing Nurtec ODT volume and access for patients requires significant investment. In these important initial years of product launch, our strategy has been to drive brand trial and adoption of Nurtec ODT by investing in patient support programs and working with payers to ensure patient access, which also results in payer rebates and volume discounts related to the investments we made for incremental access. We expect the investments we made in first quarter copay programs will drive volume and net revenue growth for NURTEC ODT in the rest of the year."

Dr. Coric continued, "In addition to continued success in the US market, we are excited about bringing the only ‘all-in-one’ therapy to both treat and prevent migraine to the approximately one billion migraine patients worldwide. With EU approval for rimegepant now secured and additional regulatory submissions planned in China and South Korea in the second half of 2022, we believe we are well positioned to grow future sales of NURTEC ODT outside of the US. We also look forward to providing an update on zavegepant following the submission of our NDA in the first quarter. If approved, zavegepant will be the first and only intranasal CGRP receptor antagonist, offering a rapid onset of action and an important treatment alternative for patients who experience nausea or vomiting at the time of their migraine attacks. We continue to believe our migraine franchise is unmatched and we could not be more excited about the opportunities for continued market expansion in the months and years to come."

First Quarter and Recent Business Highlights

CGRP Antagonist Platform – Milestones and Next Steps

Q1 2022 net product revenue from sales of NURTEC ODT totaled $123.6 million – NURTEC ODT has now achieved 2,000,000 prescriptions, and over 69,000 unique prescribers to date, an increase of 5,400 prescribers from the fourth quarter signaling continued traction across the prescribing community. $123.6 million in net product revenues for the quarter represents a 182% increase over Q1 2021 and a 35% decrease from net product revenues over Q4 2021. The substantial year-over-year revenue growth was due to prescription volume growth of 122% and a higher price/Rx due to increased sales of 2-packs (16-tablet count) in relation to 1-pack (8-tabletcount) sales. Sequentially, TRx volumes grew 8% vs. the fourth quarter. The sequential decrease in quarter-over-quarter net revenue was largely driven by seasonality related to renewed patient deductibles and prescription reauthorizations, and a corresponding increase in costs for patient affordability programs. The Company is providing FY 2022 net product sales guidance of $825 – $900 million and believes that a significant market opportunity for oral CGRP targeting agents exists.
Received EU approval of rimegepant 75 mg for the acute and preventive treatment of migraine, from the European Commission ("EC") – In April, the Company announced that the EC has approved rimegepant 75 mg (available as an orally dissolving tablet), intended for the prophylaxis and acute treatment of migraine; VYDURA (rimegepant) will be the commercial name for rimegepant in the EU. The full indication for VYDURA is the acute treatment of migraine with or without aura in adults and preventive treatment of episodic migraine in adults who have at least four migraine attacks per month. The EC approval will be valid in the 27 member countries of the EU as well as Iceland, Liechtenstein, and Norway and local reimbursement approval will follow. The Company had previously received positive opinion recommending the granting of a marketing authorization for rimegepant 75 mg from the Committee for Medicinal Products for Human Use in February of 2022.
Achieved broader commercial insurance coverage – In May, the Company expanded the total number of commercial lives covered to 96 percent and approximately 263 million people in all payer channels.
Demonstrated decreased opioid use in migraine patients following NURTEC ODT Therapy – In April, the Company presented findings pertaining to the benefit of NURTEC ODT in decreasing the burden of opioid use among a significant number of migraine patients in real world clinical practice. The findings were presented as a podium presentation at the American Association of Neurology (AAN) 2022 Annual Meeting. Opioid discontinuation rate after NURTEC ODT initiation was 40.5%.
Reported positive topline results from pivotal trial of NURTEC ODT for the acute treatment of migraine in China and South Korea – In February, the Company announced positive topline results from the Phase 3 clinical trial of NURTEC ODT in China and South Korea in adults for the acute treatment of migraine. Led by BioShin Limited, a subsidiary of Biohaven, the randomized, double-blind, placebo-controlled, regional, multi-center study met the co-primary endpoints evaluating the efficacy and safety of the orally dissolving tablet ("ODT") formulation of rimegepant, an oral CGRP receptor antagonist. This is the fifth positive pivotal study of rimegepant and the first to be conducted in Asia Pacific. The study met its co-primary endpoints of freedom from pain (p<0.0001) and freedom from most bothersome migraine–associated symptom ("MBS") including either nausea, phonophobia or photophobia (p<0.0001) at 2-hours following a single oral dose of rimegepant. The early onset, durable 48-hour efficacy, and favorable safety and tolerability profile were consistent with prior clinical trial results in the United States. In addition to the co-primary endpoints, NURTEC ODT preliminary data demonstrated significant relief of multiple migraine symptoms with rapid onset efficacy that was statistically superior to placebo as early as 45 minutes for both pain relief and freedom from MBS (p<0.05), at 60 minutes for return to normal function (p = 0.0023), and at 90 minutes for pain freedom (p = 0.0012). NURTEC ODT demonstrated sustained efficacy on all four of these clinically important efficacy outcomes through 48 hours. The use of rescue medication within 24 hours was significantly lower for NURTEC ODT-treated patients than for placebo (p < 0.0001). Detailed data from the study will be presented at future medical meetings to help inform ongoing and future research.
Commenced enrollment in Phase 2/3 sinusitis study – In February, the Company announced the enrollment of the first patient in the Phase 2/3 clinical trial assessing the safety and efficacy of NURTEC ODT (rimegepant) 75 mg in patients with chronic rhinosinusitis (CRS) with or without nasal polyps. The Company expects to enroll approximately 200 patients across approximately 25 sites in the United States. The primary outcome measure will be the pain/pressure/fullness score on a Numerical Rating Scale (0-10).
Commenced enrollment in Phase 2/3 temporomandibular disorder ("TMD") study – In April, the Company enrolled the first patient in the Phase 2/3 clinical trial assessing the safety and efficacy of NURTEC ODT (rimegepant) 75 mg in patients with temporomandibular disorder ("TMD"). Consistent with the sinusitis study, the Company expects to enroll approximately 200 patients across approximately 25 sites in the United States. The primary outcome measure will be the change from baseline of pain on a Numerical Rating Scale (0-10).
Published NURTEC (Rimegepant) breastfeeding clinical study in Breastfeeding Medicine – In April, the Company announced that data from a Phase 1, single-center, open-label study evaluating the excretion of a single dose of rimegepant 75 mg in the human milk of healthy lactating women was published in the peer reviewed journal, Breastfeeding Medicine. Migraine affects more than 30 million women in America, and migraine attacks may subside during pregnancy but resume within 4 weeks of childbirth. In April, the Company reported that the FDA approved a label amendment of the NURTEC ODT (rimegepant) Prescribing and Patient Information to include clinical lactation data in the Use in Specific Populations section as it relates to women who are breastfeeding.
Published real-world study highlighting increased healthcare utilization among Americans with episodic migraine have higher levels of migraine-related disability – In April, the Company announced the publication of new real-world research showing that as migraine-related disability increases, healthcare utilization also increases among Americans with episodic migraine. Targeting high disability patients with effective treatments may reduce disability and improve the cost-effectiveness of medical care among primary care and specialty providers. These findings were published in the March issue of Headache: The Journal of Head and Face Pain, the official journal of the American Headache Society.
Other Programs and Partnerships – Milestones and Next Steps

Acquired Kv7 channel platform for treatment of epilepsy and other neurologic disorders from Channel Biosciences, LLC – In February, the company announced that it had entered into a definitive agreement with Channel Biosciences, LLC, a subsidiary of Knopp Biosciences, LLC, to acquire a Kv7 channel targeting platform, adding the latest advances in ion-channel modulation to Biohaven’s growing neuroscience portfolio. BHV-7000 (formerly known as KB-3061) is the lead asset from the Kv7 platform and is a potentially best-in-class potassium channel activator with a profile suggestive of a wide therapeutic index, high selectivity, and significantly reduced GABA-ergic activity. Biohaven intends to bring BHV-7000 to the clinic in 2022 in preparation for a development program in focal epilepsy.
Entered into a worldwide license agreement with BMS for taldefgrobep alfa, a Phase 3-ready anti-myostatin adnectin for spinal muscular atrophy ("SMA") – In February, the Company announced that it entered into a worldwide license agreement with BMS for the development and commercialization rights to taldefgrobep alfa (formerly known as BMS-986089), a novel, Phase 3-ready anti-myostatin adnectin. Taldefgrobep is a muscle-targeted experimental treatment developed for neuromuscular disease and offers the opportunity for combination therapy. The in-licensing of taldefgrobep expands Biohaven’s portfolio of innovative, late-stage product candidates for the treatment of neurologic, neuroinflammatory, and psychiatric indications. Biohaven plans to initiate a Phase 3 clinical trial of taldefgrobep alfa in SMA in mid-2022.
Entered into exclusive license and research collaboration agreement with KU Leuven to develop and commercialize first-in-class TRPM3 antagonists for the treatment of chronic pain – In January, the Company announced that it entered into an exclusive global license and research agreement with the Center for Drug Design and Discovery ("CD3") and the Laboratory of Ion Channel Research ("LICR") at Katholieke Universiteit Leuven ("KU Leuven") to develop and commercialize first-in-class transient receptor potential melastatin-3 ("TRPM3") channel antagonists. BHV-2100 is the lead TRPM3 antagonist from the platform and an orally-bioavailable small molecule TRPM3 antagonist.
Expanded migraine awareness and education via key sponsorships – In April, the Company became the sole sponsor of the National Headache Foundation’s Veterans/Military Outreach program to raise awareness about migraine and elevate the discussion about the disease among active-duty military and veterans. In February, the Company partnered with Jessica Horwell on the Hardware LDN exhibit at New York Fashion Week, aiming to empower the people walking the runway and attending the show to get back to their lives. These partners and others help Biohaven achieve its mission of empowering sufferers of migraine from all backgrounds.
Global Coalition for Adaptive Research ("GCAR") announced update on Glioblastoma Adaptive Global Innovative Learning Environment ("GBM Agile") Phase 2-3 adaptive platform trial for patients with glioblastoma – In January, GCAR announced that Biohaven’s troriluzole and Vigeo Therapeutics’ VT1021 were selected to participate in GBM AGILE, a revolutionary patient-centered, adaptive platform trial for registration that tests multiple therapies for patients with newly-diagnosed and recurrent glioblastoma ("GBM"), the deadliest form of brain cancer. They will be evaluated in all patient subgroups of the trial which include newly-diagnosed methylated MGMT, newly-diagnosed unmethylated MGMT, and recurrent GBM. Troriluzole and VT1021 were the fourth and fifth arms to join the trial, respectively. GBM AGILE allows multiple drugs from different pharmaceutical companies to be evaluated simultaneously and/or over time against a common standard of care control.
Corporate Updates:

Appointed Irina Antonijevic, M.D., Ph.D. to Board of Directors – In April, the Company announced the appointment of Irina Antonijevic, M.D., Ph.D. to its Board of Directors starting May 1, 2022. Dr. Antonijevic is currently Chief Medical Officer ("CMO") and Head of R&D at Triplet Therapeutics, a company developing novel therapeutics for repeat expansion disorders such as Huntington’s disease, spinocerebellar ataxias and Myotonic Dystrophy. Prior to that, she served as VP of Translational Medicine and Development at Wave Life Sciences, CMO at vasopharm GmbH, developing a treatment for severe traumatic brain injury, and Head of Early Development, MS, Neurology and Ophthalmology at Sanofi Genzyme. Dr. Antonijevic has been a member of the supervisory board of 4SC AG since 2012, and of Paion AG from 2017 through early 2022. Dr. Antonijevic is board certified in Psychiatry and completed her residency in psychiatry and neurology at the Max Planck Institute for Psychiatry. Dr. Antonijevic obtained her venia legendi from the Berlin University and her PhD from the University of Edinburgh, UK.
Upcoming Milestones:

Biohaven is continuing to support the commercialization of NURTEC ODT for the acute and preventive treatment of migraine, as well as develop its product candidates through clinical and preclinical programs in a number of common and rare disorders. The Company expects to reach significant pipeline milestones across its platforms in the coming quarters.

Biohaven expects to:

Continue to advance the commercialization of NURTEC ODT (rimegepant) for the acute and preventive treatment of migraine.
Submit an NDA for the acute treatment of migraine in China in the second half of 2022.
Report topline of troriluzole in Spinocerebellar Ataxia in mid-2022.
Report topline of verdiperstat in ALS in the second half of 2022.
Complete enrollment in Phase 3 study of troriluzole in Obsessive-Compulsive Disorder in the second half of 2022.
Enroll first patient in Phase 3 spinal muscular atrophy study with taldefgrobep alfa in mid-2022.
Enroll first patient in Phase 1 focal epilepsy study with BHV-7000 (Kv7) in the second half of 2022.
Capital Position:

Cash, cash equivalents, and marketable securities as of March 31, 2022, were $602.5 million, excluding $5.3 million of restricted cash, compared to $364.6 million as of December 31, 2021. On January 4, 2022, we received $500.0 million in upfront proceeds from Pfizer relating to the strategic collaboration arrangement, consisting of $150.0 million cash and $350.0 million in proceeds from the purchase of Biohaven common shares at a 25% market premium. We also have $125.0 million in non-dilutive committed capital from our credit facility with Sixth Street.

First Quarter 2022 Financial Highlights

Product Revenue, Net: Net product revenue was $123.6 million for the three months ended March 31, 2022, compared to $43.8 million for the three months ended March 31, 2021. The increase of $79.8 million in net product revenue is due to both increased NURTEC ODT sales volume and improvements in net price realization due to decreases in sales allowances during the three months ended March 31, 2022, compared to the three months ended March 31, 2021. Sales allowances and accruals mostly consisted of patient affordability programs, distribution fees and rebates.

Collaboration and Other Revenue: Collaboration and other revenue was $195.3 million for the three months ended March 31, 2022. No collaboration and other revenue was recognized for the three months ended March 31, 2021. The collaboration and other revenue recognized during the three months ended March 31, 2022 was primarily due to $194.4 million recognized upon the satisfaction of our performance obligation for the delivery of the license and sublicense to commercialize Rimegepant outside the U.S. as part of our Collaboration Agreement with Pfizer.

Research and Development ("R&D") Expenses: R&D expenses, including non-cash share-based compensation costs, were $119.1 million for the three months ended March 31, 2022, compared to $107.1 million for the three months ended March 31, 2021. The increase of $12.0 million was primarily due to increased personnel costs partially offset by decreased program expenses. Non-cash share-based compensation expense was $34.0 million for the three months ended March 31, 2022, an increase of $13.9 million as compared to the same period in 2021.

Selling, General and Administrative ("SG&A") Expenses: SG&A expenses, including non-cash share-based compensation costs, were $227.2 million for the three months ended March 31, 2022, compared to $159.5 million for the three months ended March 31, 2021. The increase of $67.7 million was primarily due to increases in spending to support increased commercial sales of NURTEC ODT, including the launch of NURTEC ODT for the preventative treatment of migraine which was approved by the FDA in May of 2021. Less than half of the SG&A expense was for commercial organization personnel costs, excluding non-cash share-based compensation expense. Non-cash share-based compensation expense was $47.9 million for the three months ended March 31, 2022, an increase of $19.2 million as compared to the same period in 2021.

Net Loss: Biohaven reported a net loss attributable to common shareholders for the three months ended March 31, 2022, of $209.1 million, or $2.97 per share, compared to $265.0 million, or $4.27 per share for the same period in 2021. Non-GAAP adjusted net loss for the three months ended March 31, 2022 was $114.0 million, or $1.62 per share, compared to $201.4 million, or $3.25 per share for the same period in 2021. These non-GAAP adjusted net loss and non-GAAP adjusted net loss per share measures, more fully described below under "Non-GAAP Financial Measures," exclude non-cash share-based compensation charges, non-cash interest expense related to the accounting for mandatorily redeemable preferred shares and liability related to sale of future royalties, changes in the fair value of derivatives and gains or losses from equity method investment. A reconciliation of the GAAP financial results to non-GAAP financial results is included in the tables below.

Non-GAAP Financial Measures
This press release includes financial results prepared in accordance with accounting principles generally accepted in the United States (GAAP), and also certain non-GAAP financial measures. In particular, Biohaven has provided non-GAAP adjusted net loss and adjusted net loss per share, adjusted to exclude the items below. Non-GAAP financial measures are not an alternative for financial measures prepared in accordance with GAAP. However, Biohaven believes the presentation of non-GAAP adjusted net loss and adjusted net loss per share, when viewed in conjunction with GAAP results, provides investors with a more meaningful understanding of ongoing operating performance. These measures exclude (i) non-cash share-based compensation, which is substantially dependent on changes in the market price of common shares, (ii) interest expense related to the accounting for our mandatorily redeemable preferred shares and liability related to sale of future royalties, which are in excess of the actual interest owed, (iii) changes in the fair value of derivative liability, which does not correlate to actual cash payment obligations in the relevant periods, and (iv) gains or losses from equity method investment, which are non-cash and based on the financial results and valuation of another company that we did not manage or control.

Biohaven believes the presentation of these non-GAAP financial measures provides useful information to management and investors regarding Biohaven’s results of operations. When GAAP financial measures are viewed in conjunction with these non-GAAP financial measures, investors are provided with a more meaningful understanding of Biohaven’s ongoing operating performance and are better able to compare Biohaven’s performance between periods. In addition, these non-GAAP financial measures are among those indicators Biohaven uses as a basis for evaluating performance, and planning and forecasting future periods. These non-GAAP financial measures are not intended to be considered in isolation or as a substitute for GAAP financial measures. A reconciliation between these non-GAAP measures and the most directly comparable GAAP measures is provided later in this press release.

On May 10, 2022 Intra-Cellular Therapies, Inc. (Nasdaq: ITCI), a biopharmaceutical company focused on the development and commercialization of therapeutics for central nervous system (CNS) disorders, reported its financial results for the first quarter ended March 31, 2022 and provided a corporate update (Press release, Intra-Cellular Therapies, MAY 10, 2022, View Source [SID1234614056]).

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"We are encouraged by the robust uptake of CAPLYTA in the first full quarter following our late December 2021 launch in bipolar depression and are confident in our ability to deliver continued strong growth and to improve the lives of patients. We continue to advance our pipeline, including our lumateperone programs in major depressive disorder (MDD) and mixed features," said Dr. Sharon Mates, Chairman and CEO of Intra-Cellular Therapies.

First Quarter Financial Highlights:

Total revenues were $35.0 million for the first quarter of 2022, compared to $15.9 million of total revenues for the first quarter of 2021. Net product revenues of CAPLYTA were $34.8 million for the first quarter of 2022, compared to $15.6 million in net product revenues of CAPLYTA for the same period in 2021, representing a year-over-year increase of 123% and a 36% increase over the fourth quarter of 2021.

Cost of product sales were $3.2 million in the first quarter of 2022, compared to $1.5 million for the first quarter of 2021.

Research and development (R&D) expenses for the first quarter of 2022 were $29.0 million, compared to $15.1 million for the first quarter of 2021. This increase is due to higher lumateperone clinical trial and non-clinical related costs and an increase in non-lumateperone project costs.

Selling, general and administrative (SG&A) expenses were $75.5 million for the first quarter of 2022, compared to $52.6 million for the first quarter of 2021. This increase is primarily due to an increase in commercialization, marketing and labor related costs.

Net loss for the quarter ended March 31, 2022 was $72.1 million, compared to a net loss of $52.7 million for the quarter ended March 31, 2021.

Cash, cash equivalents, restricted cash and investment securities totaled $773.2 million at March 31, 2022, compared to $413.7 million at December 31, 2021. On January 7, 2022, we completed a public offering of our common stock in which we sold approximately 10.95 million shares of common stock for aggregate gross proceeds of $460.0 million and net proceeds, after deducting underwriting discounts and commissions and offering expenses, of approximately $433.7 million.

COMMERCIAL HIGHLIGHTS

CAPLYTA launched in bipolar depression immediately following its U.S. Food and Drug Administration (FDA) approval in late December 2021. CAPLYTA is the first and only FDA-approved treatment for depressive episodes associated with bipolar I or II disorder (bipolar depression) in adults as monotherapy and as adjunctive therapy with lithium or valproate.

Significant inflection in both new and total prescriptions reflecting robust growth following approval in bipolar depression. First quarter CAPLYTA new and total prescriptions increased by 63% and 45%, respectively, versus the fourth quarter of 2021. First quarter CAPLYTA new and total prescriptions increased by 154% and 134%, respectively, versus the first quarter of 2021.

New-to-brand prescriptions, representing new CAPLYTA patient starts, have increased by approximately 300% following bipolar depression approval. New-to-brand prescriptions are considered a key leading indicator of growth during the launch phase, reflecting early adoption by prescribers. These encouraging uptake trends have been accompanied by positive physician receptivity to CAPLYTA.

CAPLYTA maintained broad coverage in the Medicare Part D and Medicaid channels, with greater than 98% of lives covered and expanded coverage in the commercial channel to over 80% of lives covered. Our LytaLink patient support program continues to be very effective in supporting patient access.

CLINICAL HIGHLIGHTS

Lumateperone:

Received approval by the FDA for two new dosage strengths of CAPLYTA, 10.5 mg and 21 mg capsules, to provide dosage recommendations for patients concomitantly taking strong or moderate CYP3A4 inhibitors, and 21 mg for patients with moderate or severe hepatic impairment (Child-Pugh class B or C). This strengthens CAPLYTA’s overall profile even further by expanding the appropriate patient base within the highly prevalent conditions of bipolar disorder and schizophrenia.

Adjunctive MDD program: Patient enrollment in pivotal studies 501 and 502 is ongoing. These are Phase 3 double blind, placebo-controlled, 6-week global studies evaluating lumateperone 42 mg as adjunctive treatment to anti-depressants. The primary endpoint is change from baseline versus placebo on the MADRS total score at week 6, and the CGI-S scale is the key secondary endpoint. We expect to file a supplemental New Drug Application (sNDA) with the FDA for lumateperone as an adjunctive therapy to antidepressants for the treatment of MDD in 2024.

Mixed Features program: Clinical conduct is ongoing in Study 403, a global clinical trial evaluating lumateperone 42 mg in patients with MDD and in patients with bipolar depression who exhibit mixed features. We expect to complete clinical conduct in this Study in the second half of 2022.

Lumateperone Long Acting Injectable (LLAI) formulation: Initial clinical conduct in our Phase 1 single ascending study has been completed, and we are encouraged by the safety and tolerability results we have seen to date. We are exploring alternate sites of injection with the current formulation as well as progressing the development of other formulations. The goal of our program is to develop LLAI formulations that are effective, safe and well-tolerated with treatment durations of one month and longer. Together, these Phase 1 studies will assist us in designing formulation and dosing strategies for our efficacy studies.

Other Programs:

ITI-1284-ODT-SL program: ITI-1284 ODT-SL Phase 1 studies are either ongoing or planned, including food effect and brain-imaging studies. We expect to commence clinical conduct in our agitation in patients with probable Alzheimer’s disease program in 2022, followed by additional studies in dementia-related psychosis and certain depressive disorders in the elderly. We have previously completed single and multiple ascending dose studies in healthy young and elderly subjects, demonstrating rapid absorption and excellent drug exposure, allowing doses to be selected for our next studies.

Phosphodiesterase type I inhibitor (PDE1) program: Lenrispodun (ITI-214) is our lead compound in this program. We expect to initiate patient enrollment/clinical conduct in our lenrispodun Phase 2 clinical trial for the treatment of Parkinson’s disease in the first half of 2022.

In preclinical studies, we have shown that PDE1 inhibitors can inhibit the recruitment of immune cells such as microglia and macrophages into tumors, thereby altering the tumor microenvironment. We have shown that lenrispodun can potentiate the action of PD-1 inhibitors in various models of colorectal, kidney, breast and glioblastoma cancers. Recently, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, we presented preclinical data describing the antitumor effects of PDE1 inhibitors when administered in conjunction with checkpoint inhibitor immunotherapy in an animal model of breast cancer. Additional data from this program will be presented at upcoming conferences this year.

ITI-333 program in Opioid Use Disorder: Following the positive results from our Phase 1 single ascending dose study evaluating the safety, tolerability and pharmacokinetics of ITI-333 in healthy volunteers, our plan is to advance the development of ITI-333 with neuroimaging studies, followed by a multiple ascending dose study.

Conference Call and Webcast Details

The Company will host a live conference call and webcast today at 8:30 AM Eastern Time to discuss the Company’s financial results and provide a corporate update. The live webcast and subsequent replay may be accessed by visiting the Company’s website at www.intracellulartherapies.com. Please connect to the Company’s website at least 5-10 minutes prior to the live webcast to ensure adequate time for any necessary software download. Alternatively, please call 1-(844) 835-6563 (U.S.) or 1-(970) 315-3916 (international) to listen to the live conference call. The conference ID number for the live call is 9526447. Please dial in approximately 10 minutes prior to the call.

CAPLYTA (lumateperone) is indicated in adults for the treatment of schizophrenia and depressive episodes associated with bipolar I or II disorder (bipolar depression) as monotherapy and as adjunctive therapy with lithium or valproate. CAPLYTA is available in 42 mg capsules.

Important Safety Information

Boxed Warnings:

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. CAPLYTA is not approved for the treatment of patients with dementia-related psychosis.

Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adults in short-term studies. All anti-depressant-treated patients should be closely monitored for clinical worsening, and for emergence of suicidal thoughts and behaviors. The safety and effectiveness of CAPLYTA have not been established in pediatric patients.

Contraindications: CAPLYTA is contraindicated in patients with known hypersensitivity to lumateperone or any components of CAPLYTA. Reactions have included pruritus, rash (e.g., allergic dermatitis, papular rash, and generalized rash), and urticaria.

Warnings & Precautions: Antipsychotic drugs have been reported to cause:

Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis, including stroke and transient ischemic attack. See Boxed Warning above.

Neuroleptic Malignant Syndrome (NMS), which is a potentially fatal reaction. Signs and symptoms include: high fever, stiff muscles, confusion, changes in breathing, heart rate, and blood pressure, elevated creatinine phosphokinase, myoglobinuria (and/or rhabdomyolysis), and acute renal failure. Patients who experience signs and symptoms of NMS should immediately contact their doctor or go to the emergency room.

Tardive Dyskinesia, a syndrome of uncontrolled body movements in the face, tongue, or other body parts, which may increase with duration of treatment and total cumulative dose. TD may not go away, even if CAPLYTA is discontinued. It can also occur after CAPLYTA is discontinued.

Metabolic Changes, including hyperglycemia, diabetes mellitus, dyslipidemia, and weight gain. Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma or death, has been reported in patients treated with antipsychotics. Measure weight and assess fasting plasma glucose and lipids when initiating CAPLYTA and monitor periodically during long-term treatment.

Leukopenia, Neutropenia, and Agranulocytosis (including fatal cases). Complete blood counts should be performed in patients with pre-existing low white blood cell count (WBC) or history of leukopenia or neutropenia. CAPLYTA should be discontinued if clinically significant decline in WBC occurs in absence of other causative factors.

Decreased Blood Pressure & Dizziness. Patients may feel lightheaded, dizzy or faint when they rise too quickly from a sitting or lying position (orthostatic hypotension). Heart rate and blood pressure should be monitored and patients should be warned with known cardiovascular or cerebrovascular disease. Orthostatic vital signs should be monitored in patients who are vulnerable to hypotension.

Falls. CAPLYTA may cause sleepiness or dizziness and can slow thinking and motor skills, which may lead to falls and, consequently, fractures and other injuries. Patients should be assessed for risk when using CAPLYTA.

Seizures. CAPLYTA should be used cautiously in patients with a history of seizures or with conditions that lower seizure threshold.

Potential for Cognitive and Motor Impairment. Patients should use caution when operating machinery or motor vehicles until they know how CAPLYTA affects them.

Body Temperature Dysregulation. CAPLYTA should be used with caution in patients who may experience conditions that may increase core body temperature such as strenuous exercise, extreme heat, dehydration, or concomitant anticholinergics.

Dysphagia. CAPLYTA should be used with caution in patients at risk for aspiration.

Drug Interactions: CAPLYTA should not be used with CYP3A4 inducers. Dose reduction is recommended for concomitant use with strong CYP3A4 inhibitors (10.5 mg) or moderate CYP3A4 inhibitors (21 mg).

Special Populations: Newborn infants exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. Breastfeeding is not recommended. Dose reduction is recommended for patients with moderate or severe hepatic impairment (21 mg).

Adverse Reactions: The most common adverse reactions in clinical trials with CAPLYTA vs. placebo were somnolence/sedation, dizziness, nausea, and dry mouth.

Please click here to see full Prescribing Information including Boxed Warning.

About CAPLYTA (lumateperone)

CAPLYTA 42 mg is an oral, once daily atypical antipsychotic approved in adults for the treatment of schizophrenia and depressive episodes associated with bipolar I or II disorder (bipolar depression) as monotherapy and as adjunctive therapy with lithium or valproate. While the mechanism of action of CAPLYTA is unknown, the efficacy of CAPLYTA could be mediated through a combination of antagonist activity at central serotonin 5-HT2A receptors and postsynaptic antagonist activity at central dopamine D2 receptors.

Lumateperone is being studied for the treatment of major depressive disorder, and other neuropsychiatric and neurological disorders