On November 9, 2022 Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) (the "Company") reported financial results for the third quarter of 2022 (Press release, Ionis Pharmaceuticals, NOV 9, 2022, View Source [SID1234623538]). Financial results are summarized below :

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!

Financial Highlights

Revenue increased 20% for the third quarter of 2022 and 18% on a year-to-date basis compared to the same periods last year driven by significant partner payments earned across multiple programs
Non-GAAP operating expenses increased 5% for the third quarter of 2022 and 13% on a year-to-date basis compared to the same periods last year driven by advancing Phase 3 pipeline
Entered into a long-term lease in October 2022 to construct a new manufacturing facility supporting continued growth
Entered into a sale-leaseback transaction in October 2022 for several real estate assets, generating net proceeds of $240 million plus full funding to expand R&D campus
Reaffirmed 2022 P&L guidance; increased cash and investments guidance to approximately $2.0 billion
Late-Stage Pipeline Highlights

Presented positive data from the Phase 3 NEURO-TTRansform study of eplontersen in patients with polyneuropathy caused by hereditary TTR amyloidosis; on track to file U.S. New Drug Application this year
Expanded enrollment in the Phase 3 CARDIO-TTRansform study of eplontersen in patients with ATTR cardiomyopathy; data still expected first half of 2025
NDA for tofersen was accepted and granted priority review by the FDA; Prescription Drug User Fee Act date of April 25, 2023
Initiated CORE2, a confirmatory Phase 3 study of olezarsen in patients with severe hypertriglyceridemia (SHTG)
Initiated ESSENCE, a supporting Phase 3 study of olezarsen in patients with SHTG or hypertriglyceridemia and cardiovascular disease
Mid-Stage Pipeline Highlights

GSK presented positive end of study data from the Phase 2b B-Clear study of bepirovirsen demonstrating potential for functional cures in patients with chronic hepatitis B; GSK plans to advance bepirovirsen into Phase 3 development in the first half of 2023
Presented positive data from the Phase 2 study of IONIS-FB-LRx in patients with immunoglobulin A nephropathy; Roche plans to advance IONIS-FB-LRx into Phase 3 development in the first half of 2023
Bayer presented positive data from the Phase 2b study of fesomersen in patients with end-stage renal disease; Ionis regained rights to fesomersen from Bayer and is assessing next steps
Roche presented the Phase 2 GENERATION HD2 study design of tominersen in Huntington’s disease patients; Roche plans to begin enrollment in early 2023
Reported ION449 (AZD8233) targeting PCSK9 met the primary endpoint in Phase 2b SOLANO study in patients with hypercholesterolemia; based on pre-specified efficacy criteria, AstraZeneca is not advancing ION449
"We have made significant progress on our key priorities this year, building our commercial pipeline, delivering an abundance of new medicines to the market and expanding and diversifying our technology. We delivered positive data from eight key programs, positioning us to potentially add two new marketed medicines to our portfolio and expand our rich Phase 3 pipeline to eight medicines next year. Additionally, we have recently begun work on a manufacturing facility to support our pipeline growth," said Brett P. Monia, Ph.D., chief executive officer of Ionis. "As we advance our near-term opportunities, including filing the NDA this year for eplontersen, and expanding our rich late-stage pipeline, we are well positioned to drive increasing value for all stakeholders."

Total revenue for the three and nine months ended September 30, 2022 increased 20 percent and 18 percent compared to the same periods last year, respectively. The increase was driven by significant payments Ionis earned across multiple partnered programs. R&D revenue for the nine months ended September 30, 2022 included $85 million from Biogen for advancing several neurology disease programs, $63 million from Roche for licensing and advancing IONIS-FB-LRx and $55 million from AstraZeneca for its share of the global Phase 3 development costs for eplontersen.

Commercial revenue for the three and nine months ended September 30, 2022 decreased 15 percent and 13 percent compared to the same periods last year, respectively. SPINRAZA royalties for the three and nine months ended September 30, 2022 decreased 7 percent and 12 percent compared to the same periods last year, respectively. In the U.S., SPINRAZA sales were flat in the first nine months of 2022 compared to the same period last year. Outside of the U.S. SPINRAZA royalties were lower due to lower SPINRAZA product sales primarily due to decreased pricing, foreign currency exchange and competition. TEGSEDI and WAYLIVRA revenue was also lower due to the shift to distribution fees in 2021.

Operating Expenses

Ionis’ non-GAAP operating expenses increased for the three and nine months ended September 30, 2022 compared to the same periods in 2021, in line with expectations. For both periods, higher R&D expenses were driven by the expanded number of Phase 3 studies the Company is conducting, which doubled from three to six studies in 2021. SG&A expenses increased for the three months ended September 30, 2022 compared to the same period last year driven by Ionis’ go-to-market activities for eplontersen, donidalorsen and olezarsen. SG&A expenses were lower for the nine months ended September 30, 2022 compared to the same period last year largely due to the substantial savings the Company achieved from integrating Akcea and restructuring its commercial operations in 2021.

Balance Sheet

As of September 30, 2022, Ionis had cash, cash equivalents and short-term investments of $2.0 billion, compared with $2.1 billion at December 31, 2021. Ionis’ debt obligations and working capital did not change significantly from December 31, 2021 to September 30, 2022.

In October 2022, Ionis entered into a sale and leaseback transaction for several of its real estate assets. Under the agreement, Ionis will receive net proceeds of approximately $240 million plus full funding to expand the Company’s R&D campus. The net proceeds reflect the Company’s extinguishment of its mortgage debt for the related properties. Ionis’ fourth quarter financial results will reflect the impact this transaction.

2022 Financial Guidance

The Company reaffirmed its full year 2022 guidance for total revenue, operating expenses and net loss, on a non-GAAP basis. The Company’s 2022 operating expense guidance, compared to the prior year, includes increasing R&D expenses between 25% and 30% and consistent SG&A expenses. Ionis expects to recognize a substantial gain on the sale of its real estate assets in the fourth quarter. The gain will not impact the Company’s non-GAAP results since the sale was non-recurring and not part of the Company’s normal business operations.

The Company increased its full year 2022 cash and investments guidance to approximately $2.0 billion from the previous guidance of $1.7 billion.

"Our strong year-to-date results, including year-over-year revenue growth of nearly 20 percent, keep us on track to meet our 2022 P&L guidance," said Elizabeth L. Hougen, chief financial officer of Ionis. "Additionally, we recently bolstered our balance sheet when we unlocked net proceeds of approximately $240 million plus full funding to expand our R&D campus by capitalizing on the favorable life sciences real estate market and monetizing several of our facilities through a sale and leaseback transaction. As a result, we are increasing our 2022 cash and short-term investment guidance to approximately $2 billion."

Webcast

Management will host a conference call and webcast to discuss Ionis’ third quarter 2022 results at 11:30 a.m. Eastern time on Wednesday, November 9, 2022. Interested parties may access the webcast here. A webcast replay will be available for a limited time at the same address. To access the Company’s third quarter 2022 earnings slides click here.

On November 9, 2022 Alligator Bioscience AB ("Alligator") (Nasdaq Stockholm: ATORX) and Aptevo Therapeutics ("Aptevo") (Nasdaq: APVO) reported the publication of a peer-reviewed article highlighting preclinical data that demonstrates a positive safety and anti-tumor activity profile in both in vitro and in vivo studies for ALG (Press release, Alligator Bioscience, NOV 9, 2022, View Source [SID1234623537]).APV-527, a novel second generation 4-1BB agonistic bispecific antibody that is designed to stimulate 4-1BB function only when co-engaged with the tumor-associated antigen 5T4.

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

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

                  Schedule Your 30 min Free Demo!

The publication in Molecular Cancer Therapeutics, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), includes data provided in the companies’ investigational new drug (IND) application to the US Food and Drug Administration (FDA) supporting the advancement of ALG.APV-527 into the clinic for evaluation in the treatment of multiple solid tumor types.

The article, entitled "The bispecific tumor antigen-conditional 4-1BB × 5T4 agonist, ALG.APV-527, mediates strong T cell activation and potent anti-tumor activity in preclinical studies", demonstrates how the design, epitope, and molecular properties of ALG.APV-527 translate into a potentially safe and potent anti-cancer therapeutic both in vitro and in vivo for the treatment of multiple solid tumor types. The preclinical functional data presented demonstrate that ALG.APV-527 has the potential to activate key immune cell populations such as T cells and NK cells within the tumor microenvironment. Of particular importance is the favorable safety profile, where the preclinical data demonstrates a potentially wider therapeutic window for ALG.APV-527 compared to first generation 4-1BB agonists.

The full article is available in print and online via this link.

"We are pleased to see this peer-reviewed validation of our preclinical studies for ALG.APV-527 as we work together with our partners at Alligator to advance the compound into Phase 1 evaluation here in the US," said Marvin White, President, and CEO of Aptevo. "We strongly believe ALG.APV-527 has the potential to positively impact the treatment paradigm for cancer patients with solid tumors and look forward to initiating our clinical program and advancing that promise."

"The publication of this scientific paper in the prestigious Molecular Cancer Therapeutics journal is an exciting achievement and deserved recognition for the hard work of the scientific teams at Alligator and Aptevo," said Søren Bregenholt, PhD, CEO of Alligator Bioscience. "The preclinical safety studies suggest that ALG.APV-527 displays a wide therapeutic window which, given the unmet need for therapies in several cancer indications that express 5T4, means it has the potential to meaningfully improve response rates seen with the current standard of care in these indications."

In September 2022, the FDA issued a "may proceed" notification for the ALG.APV-527 IND. Alligator and Aptevo are working rapidly to initiate a multi-center Phase 1 trial in the US to evaluate ALG.APV-527 in the treatment of multiple solid tumor types expressing the tumor antigen 5T4.

About ALG.APV-527
ALG.APV-527 is an antibody with dual function: tumor-binding and 4-1BB immunomodulatory agonist effects. This has the potential to be clinically important because 4-1BB has the ability to stimulate the immune cells (antitumor-specific T cells) involved in tumor control, making 4-1BB a particularly compelling target for cancer immunotherapy. Preclinical results, presented at the Society of Immunotherapy Cancer’s 2021 Annual Meeting, highlighted the differentiated design of the molecule that minimizes systemic immune activation, allowing for highly efficacious tumor-specific responses as demonstrated by potent activity in in vitro models. Alligator and Aptevo are working rapidly to advance ALG.APV-527 into Phase 1 clinical development in the US.

The information was submitted for publication, through the agency of the contact persons set out below at 5:15 p.m. CET on November 9, 2022.

On November 9, 2022 Interim Reported that for the First Nine Months Ended September 30, 2022 (Press release, Genmab, NOV 9, 2022, View Source [SID1234623536])

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!

Highlights

Genmab revenue increased 60% compared to the first nine months of 2021, to DKK 9,368 million
Genmab improves its 2022 financial guidance
"During the first nine months of the year we continued to build on Genmab’s consistent track record of success. We have strengthened our pipeline, our team and our financial foundation is even more robust. We are pleased with the recent U.S. and European regulatory submissions for epcoritamab. These submissions are an important step in potentially bringing epcoritamab to people living with certain hematologic malignancies who are in need of a new treatment option," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

Financial Performance First Nine Months of 2022

Net sales of DARZALEX by Janssen Biotech, Inc. (Janssen) were USD 5,894 million in the first nine months of 2022 compared to USD 4,378 million in the first nine months of 2021, an increase of USD 1,516 million, or 35%.
Royalty revenue was DKK 8,207 million in the first nine months of 2022 compared to DKK 4,698 million in the first nine months of 2021, an increase of DKK 3,509 million, or 75%. The increase in royalties was driven by higher net sales of DARZALEX, Kesimpta and TEPEZZA and a higher average exchange rate between the USD and DKK.
Revenue was DKK 9,368 million for the first nine months of 2022 compared to DKK 5,863 million for the first nine months of 2021. The increase of DKK 3,505 million, or 60%, was primarily driven by higher DARZALEX, Kesimpta and TEPEZZA royalties achieved under our collaborations with Janssen, Novartis Pharma AG (Novartis) and Roche, respectively, an increase in Tivdak collaboration revenue, and reimbursement revenue driven by higher activities under our collaboration agreements with BioNTech SE (BioNTech), partly offset by milestones achieved under our collaborations with Janssen and AbbVie in the first nine months of 2021.
Operating expenses were DKK 5,676 million in the first nine months of 2022 compared to DKK 3,654 million in the first nine months of 2021. The increase of DKK 2,022 million, or 55%, was driven by the continued advancement of epcoritamab and multiple pipeline projects, an increase in team members to support Tivdak post launch and expansion of our product pipeline, and the continued development of Genmab’s commercialization and broader organizational capabilities and infrastructure.
Operating profit was DKK 3,692 million in the first nine months of 2022 compared to DKK 2,209 million in the first nine months of 2021.
Net financial items was income of DKK 2,681 million for the first nine months of 2022 compared to income of DKK 808 million in the first nine months of 2021. The increase of DKK 1,873 million was primarily driven by net foreign exchange rate gains due to the USD strengthening against the DKK.
Epcoritamab Regulatory Update
There were two regulatory submissions for epcoritamab in the second half of 2022. Genmab submitted a biologics license application (BLA) to the U.S. Food and Drug Administration (U.S. FDA) for subcutaneous (SC) epcoritamab for the treatment of patients with relapsed/refractory large B-cell lymphoma (LBCL) after two or more lines of systemic therapy. Additionally, AbbVie submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for SC epcoritamab for the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy, which has been validated by the EMA. Both submissions were supported by results from the LBCL cohort of the pivotal EPCORE NHL-1 open-label, multi-center trial evaluating the safety and preliminary efficacy of epcoritamab in patients with relapsed, progressive or refractory CD20+ mature B-cell non-Hodgkin lymphoma (B-NHL), including DLBCL.

Outlook
As announced in Company Announcement No. 54, Genmab is improving its 2022 financial guidance published on August 8, 2022, driven primarily by the positive foreign exchange rate impact on our royalty revenue, and the continued strong performance of DARZALEX net sales.

Conference Call
Genmab will hold a conference call in English to discuss the results for the first nine months of 2022 today, Wednesday, November 9, at 6:00 pm CET, 5:00 pm GMT or 12:00 pm EST. To join the call please use the below registration link. Registered participants will receive an email with a link to access dial-in information as well as a unique personal PIN: https://register.vevent.com/register/BI2f752c494cf441f8b2fd8379c5219dc7. A live and archived webcast of the call and relevant slides will be available at www.genmab.com/investors.

On November 9, 2022 Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) and Royalty Pharma plc (Nasdaq: RPRX) reported that Royalty Pharma has acquired a royalty interest in Amgen’s olpasiran from Arrowhead for $250 million in cash upfront plus up to $160 million in additional payments contingent on the achievement of certain clinical, regulatory, and sales milestones (Press release, Arrowhead Pharmaceuticals, NOV 9, 2022, View Source [SID1234623535]).

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!

Olpasiran is a small interfering RNA (siRNA) originally developed by Arrowhead using its proprietary Targeted RNAi Molecule, or TRiM, platform and licensed to Amgen in 2016. It is designed to lower levels of lipoprotein(a) (Lp(a)), a genetically-determined independent risk factor for cardiovascular disease, and is entering a Phase 3 cardiovascular outcomes study to determine whether treatment with olpasiran can reduce the risk of cardiovascular events in patients with atherosclerotic cardiovascular disease and high levels of Lp(a). Phase 2 study results from the OCEAN(a)-DOSE study were presented at the American Heart Association Scientific Sessions 2022, where olpasiran demonstrated a significant and sustained reduction in Lp(a) levels over 36 weeks. These data were simultaneously published in the New England Journal of Medicine on November 6, 2022.

"We are pleased to reach this agreement with Royalty Pharma, which is recognized as a leader in funding innovation across life sciences," said Chris Anzalone, Ph.D., Arrowhead’s President and Chief Executive Officer. "Olpasiran, which we developed and licensed to Amgen for further clinical development and commercialization, has the potential to benefit millions of patients worldwide by reducing the risk of cardiovascular disease. The early monetization of this potential royalty stream validates olpasiran’s significant potential and enables us to continue to invest in our TRiM platform and our diverse and growing pipeline of RNAi therapeutic candidates."

"We are delighted to partner with Arrowhead, a leader in RNA interference (RNAi) therapeutics, to help them achieve their strategic objectives and fund their attractive pipeline," said Pablo Legorreta, Royalty Pharma’s founder and Chief Executive Officer. "Cardiovascular disease remains the most common cause of death worldwide despite certain treatment advances, and new therapeutic targets are greatly needed. Olpasiran is a promising late-stage treatment approach with the potential to lower lipoprotein(a), and this agreement is consistent with our strategy of acquiring innovative therapies in areas of high unmet patient need."

Royalty Pharma is acquiring Arrowhead’s entire royalty interest in olpasiran, which is a royalty up to the low double digits on worldwide net sales. Arrowhead will retain rights to the $400 million in development, regulatory, and sales milestone payments potentially due from Amgen.

Advisors

Gibson, Dunn & Crutcher acted as legal advisor to Arrowhead. Goodwin Procter, Fenwick & West and Maiwald acted as legal advisors to Royalty Pharma.

On November 9, 2022 Biohaven Ltd. (NYSE: BHVN) ("Biohaven" or the "Company"), a global clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of life-changing therapies for people with debilitating neurological and neuropsychiatric diseases, including rare disorders, reported financial results for the third quarter ended September 30, 2022, and provided a review of recent accomplishments and anticipated upcoming milestones (Press release, Biohaven Pharmaceutical, NOV 9, 2022, View Source [SID1234623533]). The reported financial results present, on a historical basis, the combined assets, liabilities, expenses and cash flows directly attributable to the Company, which have been prepared from Biohaven Pharmaceutical Holding Company Ltd., the former parent, consolidated financial statements and accounting records, and are presented on a stand-alone basis as if the operations had been conducted independently from the former parent.

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!

Vlad Coric, M.D., Chairman and Chief Executive Officer of Biohaven, commented, "Just weeks after launching in October as a new publicly traded company and separate independent entity as part of the merger agreement with Pfizer, we continued to advance our late stage clinical development programs and substantially enhanced our resources by raising gross proceeds of approximately $301.9 million in a public financing that drew support from a breadth of longstanding and new Biohaven investors. We are well positioned with an outstanding drug development team, a deep late-stage pipeline and a strong capital position to favorably position us to accelerate development across our portfolio."

Dr. Coric continued, "Our Kv7 platform, with its vast potential to address epilepsy and neuropsychiatric indications, is being prioritized by the team with the goal of at least one Phase 2/3 study start in 2023. We also continue to make progress with our Phase 3 study evaluating taldefgrobep alfa in patients with spinal muscular atrophy, as well as with our Phase 3 study evaluating troriluzole in patients with OCD. Finally, our discovery efforts remain a key pillar of our pipeline formation strategy; with IND-enabling studies underway across several programs, we expect to provide updates on programs like TRPM3, a potential breakthrough, non-opioid treatment option for pain, and other earlier stage protein degrader programs in the coming months and years. Our unwavering commitment to patients continues propelling us forward and we cannot wait to deliver additional therapeutic breakthrough medicines to drive outcomes for patients, shareholders and employees."

Third Quarter and Recent Business Highlights:
Company launch – On October 3, 2022, Biohaven Ltd. began operating as a separate independent entity in connection with the merger agreement entered into with Pfizer Inc. in May 2022. As of October 4, 2022, Biohaven Ltd. commenced regular way trading under the symbol "BHVN" on the New York Stock Exchange as an independent, publicly traded company focused on delivering innovative life-changing treatments for neurological and neuropsychiatric diseases, including rare disorders, and leveraging its proven drug development capabilities and proprietary technology platforms to advance a pipeline of best-in-class therapies. The Company, led by Vlad Coric, M.D. as Chairman and Chief Executive Officer, launched with approximately $257.8 million in cash and no debt.
Public offering – On October 25, 2022, the Company closed its previously announced underwritten public offering of 28,750,000 of its common shares, which includes the full exercise of the underwriters’ option to purchase 3,750,000 additional shares, at the public offering price of $10.50 per share. The gross proceeds raised in the offering, before deducting underwriting discounts and estimated expenses of the offering payable by the Company, were approximately $301.9 million. As of November 7, 2022, we had 68,160,979 common shares, without par value per share, outstanding.
Advanced Phase 1 studies for BHV-7000 – As previously reported, in the second quarter of 2022, the Company’s Clinical Trial Application for BHV-7000 was approved by Health Canada, and the Company subsequently began clinical development. BHV-7000, the lead asset from the Kv7 platform, is an activator of Kv7.2/Kv7.3, a key ion channel involved in neuronal signaling and in regulating the hyperexcitable state in epilepsy.
Advanced development of extracellular target degrader platform technology (MoDEs) for therapies across a variety of diseases including neuroscience, immunology and oncology – In October, Biohaven announced advancements in the development of its MoDE extracellular target degrader platform technology licensed from Yale University for various disease indications, including, but not limited to, neurological disorders, cancer, infectious and autoimmune diseases. Biohaven made further innovations in this ground-breaking technology with new patent applications covering additional targets and functionality.
Operationalized fully-equipped Biohaven Cambridge laboratory – In October, the Company expanded its footprint to include new laboratory space in Cambridge, Massachusetts.
Commenced enrollment in Phase 3 SMA study – In July, the Company commenced enrollment in a Phase 3 clinical trial assessing the efficacy and safety of taldefgrobep alfa in SMA. Taldefgrobep targets myostatin, a natural protein that limits skeletal muscle growth, through two mechanisms: lowering myostatin directly and blocking key downstream signaling mechanisms. The Company expects to enroll approximately 180 patients in this randomized, double-blind, placebo-controlled global trial.
Global Coalition for Adaptive Research (GCAR) commenced enrollment in Glioblastoma Adaptive Global Innovative Learning Environment (GBM Agile) Phase 2-3 adaptive platform trial for patients with glioblastoma – In July, GCAR announced the activation of Biohaven’s troriluzole in GBM AGILE, a patient-centered, adaptive platform trial for registration that tests multiple therapies for patients with newly-diagnosed and recurrent glioblastoma (GBM). GBM AGILE is an international, innovative platform trial designed to more rapidly identify and confirm effective therapies for patients with glioblastoma through response adaptive randomization. The new interventions are opening first at Henry Ford Health Cancer in Detroit under Henry Ford site Principal Investigator Dr. Tom Mikkelsen and will subsequently open at more than 40 trial sites across the United States with additional global sites to follow.
Upcoming Milestones:
Biohaven is progressing its product candidates through clinical programs in a number of common and rare disorders. The Company expects to reach significant pipeline milestones in the coming periods. Biohaven expects to:

Complete Phase 1 studies of BHV-7000 in the first half of 2023: If the Phase 1 studies are successfully completed, Biohaven expects to initiate at least one pivotal trial in patients with epilepsy in the second half of 2023.
Complete enrollment in Phase 3 study of troriluzole in OCD in 2023: Two Phase 3 randomized, double-blind, placebo-controlled studies are expected to enroll approximately 1,300 patients across nearly 200 global study sites. The Company anticipates completing enrollment in 2023.
Provide an update on troriluzole in SCA: The Company had previously reported top-line results from a Phase 3 clinical trial evaluating the efficacy and safety of its investigational therapy, troriluzole, in patients with SCA in May of 2022. While the primary endpoint, change from baseline to Week 48 on the modified functional Scale for the Assessment and Rating of Ataxia did not reach statistical significance in the overall SCA population, as there was less than expected disease progression over the course of the study, post hoc analysis of efficacy measures by genotype suggested a treatment effect in patients with the SCA Type 3 (SCA3) genotype, which represents the most common form of SCA and accounted for 41 percent of the study population. The Company intends to interact with the FDA and/or EMA in the first half of 2023. We have not yet decided on the format of such a regulatory interaction but we could seek advice through various formal or informal interactions with regulatory agencies or we could choose to submit a New Drug Application (NDA) if we believe that is warranted from the results of our ongoing post-hoc analyses.
Continue advancing Phase 3 clinical studies of taldefgrobep alfa in SMA: The Company expects to enroll approximately 180 patients in the study.
Continue advancing early discovery portfolio across multiple neuroscience and immunoscience indications: The Company’s preclinical pipeline includes molecular degraders of extracellular proteins, CD38 targeting antibody recruiting molecules (ARMs), TRP channels, TDP-43 targeting small molecules, and other undisclosed targets, including those with disease-modifying potential.
Continue pursuing formulation development work with BHVN-5500 for use in combination studies with Kv7 platform: The Company is developing BHV-5500 (lanicemine), a low-trapping NMDA receptor antagonist. One potential target indication includes Complex Regional Pain Syndrome. Other disorders of interest include post-herpetic neuralgia and diabetic peripheral neuralgia. Current work is focused on formulation development.
Capital Position:
Cash as of September 30, 2022 was $50.7 million, excluding $0.8 million of restricted cash, compared to $76.1 million as of December 31, 2021. On October 3, 2022, in connection with the closing of the acquisition of Biohaven Pharmaceutical Holding Company Ltd. by Pfizer, Biohaven Ltd. launched with a cash balance of approximately $257.8 million. On October 25, 2022, the Company closed its previously announced public offering, which resulted in net proceeds to the Company of approximately $282.8 million.

Third Quarter 2022 Financial Highlights:
Research and Development ("R&D") Expenses: R&D expenses, including non-cash share-based compensation costs, were $52.8 million for the three months ended September 30, 2022, compared to $47.0 million for the three months ended September 30, 2021. The increase of $5.9 million was primarily due to increased expenses relating to our clinical programs partially offset by decreases in our program expenses for verdiperstat. Non-cash share-based compensation expense was $9.7 million for the three months ended September 30, 2022, a decrease of $0.5 million as compared to the same period in 2021.

General and Administrative ("G&A") Expenses: G&A expenses, including non-cash share-based compensation costs, were $14.8 million for the three months ended September 30, 2022, compared to $8.5 million for the three months ended September 30, 2021. The increase of $6.3 million was primarily due to increased expenses related to accounting, legal and other professional fees associated with the Pfizer acquisition and spin-off of Biohaven Ltd. as an independent, publicly traded company. Non-cash share-based compensation expense was $7.3 million for the three months ended September 30, 2022, an increase of $2.1 million as compared to the same period in 2021.

Net Loss: Biohaven reported a net loss for the three months ended September 30, 2022, of $68.9 million, or $1.75 per share, compared to $54.4 million, or $1.38 per share, for the same period in 2021. Non-GAAP adjusted net loss for the three months ended September 30, 2022 was $49.2 million, or $1.25 per share, compared to $39.0 million, or $0.99 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 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. Net loss per share and Non-GAAP adjusted net loss per share were calculated based on the 39,368,042 shares of Biohaven Ltd. common stock distributed to Biohaven Pharmaceutical Holding Company Ltd. shareholders at the time of the Distribution, including common shares issued in connection with Biohaven Pharmaceutical Holding Company Ltd. stock options that were exercised on October 3, 2022 and common shares issued in connection with Biohaven Pharmaceutical Holding Company Ltd. restricted stock units that vested on October 3, 2022. The same number of shares is being utilized for the calculation of basic and diluted earnings per share for all periods presented prior to the Spin-Off.

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, 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) 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, and (iii) transaction-related costs incurred relating to the Company’s spin-off from Biohaven Pharmaceutical Holding Company Ltd., which are limited to a specific period of time and related to Biohaven Ltd. being established as a standalone public company.

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.