Knopp Biosciences LLC

Cash, cash equivalents, marketable securities and restricted cash as of October 2, 2024 totaled approximately $642 million Achieved positive topline trial results from pivotal trial with troriluzole in spinocerebellar ataxia (SCA) Troriluzole 200 mg QD dosed orally in patients with SCA met the study's primary endpoint on the change from baseline on the modified functional Scale for the Assessment and Rating of Ataxia (f-SARA) at 3 years in all study population genotypes Statistically significant superiority achieved on 9 consecutive, prespecified primary and secondary endpoints Both the study protocol and statistical analysis plan were submitted to, and reviewed by, the U.S. Food and Drug Administration (FDA) prior to topline data analysis Study designed in discussion with the FDA and utilized Phase 3 data and an external control of matched, untreated SCA subjects from the U.S. Clinical Research Consortium for the Study of Cerebellar Ataxia (CRC-SCA) in accordance with the FDA's Guidance on Real-World Evidence (RWE) of effectiveness CRC-SCA external control included contemporaneous natural history data gathered from 2010-2024 Planned New Drug Application (NDA) re-submission in 4Q 2024 Completed clarification meeting with CHMP Rapporteurs in 4Q 2024 and MAA documents are being updated to include the new positive BHV4157-206-RWE study data with broader indication to include all SCA genotypes Taldefgrobep alfa, a myostatin-inhibitor, Phase 3 topline data in spinal muscular atrophy (SMA) in 4Q 2024 and Phase 2 trial protocol in obesity expected in 4Q 2024 Advancing extracellular Molecular Degrader of Extracellular Protein (MoDE) programs 3 additional investigational agents expected to enter Phase 1 studies in the next quarter Anticipate Phase 1 update for BHV-1300, including subcutaneous formulation, before year-end Broad progress with TRPM3 antagonist Initiated pivotal Phase 2 trial evaluating BHV-2100, a TRPM3 antagonist, in the acute treatment of migraine Initiated separate proof of concept study with BHV-2100 in neuropathic pain Patient enrollment continues across 5 Phase 2/3 trials with Kv7 activator, BHV-7000, in epilepsy and mood disorders (bipolar and major depressive disorder (MDD)) with potential for multiple data readouts in 2025 Continued progress with antibody drug conjugate (ADC) portfolio BHV-1510 currently dosing cancer patients in Phase 1/2 study, advancing towards combination dosing of BHV-1510 with Libtayo® in 4Q 2024 Troriluzole 200 mg QD dosed orally in patients with SCA met the study's primary endpoint on the change from baseline on the modified functional Scale for the Assessment and Rating of Ataxia (f-SARA) at 3 years in all study population genotypes Statistically significant superiority achieved on 9 consecutive, prespecified primary and secondary endpoints Both the study protocol and statistical analysis plan were submitted to, and reviewed by, the U.S. Food and Drug Administration (FDA) prior to topline data analysis Study designed in discussion with the FDA and utilized Phase 3 data and an external control of matched, untreated SCA subjects from the U.S. Clinical Research Consortium for the Study of Cerebellar Ataxia (CRC-SCA) in accordance with the FDA's Guidance on Real-World Evidence (RWE) of effectiveness CRC-SCA external control included contemporaneous natural history data gathered from 2010-2024 Planned New Drug Application (NDA) re-submission in 4Q 2024 Completed clarification meeting with CHMP Rapporteurs in 4Q 2024 and MAA documents are being updated to include the new positive BHV4157-206-RWE study data with broader indication to include all SCA genotypes 3 additional investigational agents expected to enter Phase 1 studies in the next quarter Anticipate Phase 1 update for BHV-1300, including subcutaneous formulation, before year-end Initiated pivotal Phase 2 trial evaluating BHV-2100, a TRPM3 antagonist, in the acute treatment of migraine Initiated separate proof of concept study with BHV-2100 in neuropathic pain BHV-1510 currently dosing cancer patients in Phase 1/2 study, advancing towards combination dosing of BHV-1510 with Libtayo® in 4Q 2024 NEW HAVEN, Conn. , Nov. 12, 2024 /PRNewswire/ -- 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 to treat a broad range of rare and common diseases, today reported financial results for the third quarter ended September 30, 2024 , and provided a review of recent accomplishments and anticipated upcoming developments. Vlad Coric , M.D., Chairman and Chief Executive Officer of Biohaven , commented, "The team at Biohaven continues to advance multiple late and early stage assets that have the potential to change the current standard of care treatment paradigm across a number of diseases. Last quarter we announced positive topline results in our RWE trial assessing troriluzole for the treatment of spinocerebellar ataxia. Troriluzole (200 mg dosed orally) met the study's primary endpoint on the change from baseline in the f-SARA at 3 years in all study population genotypes, showed statistically significant superiority after both 1 and 2 years of treatment, and achieved statistically significant superiority on 9 consecutive, prespecified primary and secondary endpoints. This was truly a watershed moment for the Company, given the implications of potentially bending the arc of one of the most intractable neurological diseases with no currently approved treatment options. SCA robs patients of their ability to speak, walk, and take care of themselves, and often shortens lifespans and has unfortunate intergenerational implications. We were encouraged by the robust dataset gathered to date and look forward to submitting an NDA to the FDA." Dr. Coric continued, "We continue to execute across our broad pipeline including the recent initiation of our Phase 2 trial with BHV-2100 in acute migraine. Migraine burden and disability remain high despite advances in treatment; we believe our TRPM3 antagonistic approach has the potential to be a highly-effective, non-sedating, non-opioid treatment for pain and migraine. In the final months of 2024, we expect to report on a number of updates including SMA topline data and data across our MoDE™ platform including a SAD/MAD update and multiple INDs spanning β1AR for the potential treatment of dilated cardiomyopathy, galactose deficient IgA for IgA nephropathy and a further optimized IgG degrader for use in rare diseases." Third Quarter 2024 and Recent Business Highlights Achieved positive topline results in pivotal study of troriluzole in SCA - In September 2024 , the Company announced positive topline results from pivotal Study BHV4157-206-RWE demonstrating the efficacy of troriluzole on the mean change from baseline in the f-SARA after 3 years of treatment. The study achieved the primary endpoint and showed statistically significant improvements on the f-SARA at years 1 and 2. Additionally, troriluzole achieved statistically significant superiority on 9 consecutive, prespecified primary and secondary endpoints. SCA patients treated with troriluzole showed a 50-70% slowing of disease progression, representing 1.5-2.2 years delay in disease progression over the 3-year study period. The Company intends to submit an NDA to the FDA for troriluzole in the treatment of all SCA genotypes in 4Q 2024. The development program for troriluzole has been granted orphan and fast track designations, and is eligible for priority review. European Medicines Agency marketing authorization remains under review and Biohaven completed a clarification meeting with CHMP Rapporteurs in 4Q 2024. MAA documents are being updated to include the new positive BHV4157-206-RWE study data with broader indication to include all SCA genotypes. Initiated Phase 2 trial evaluating BHV-2100 in the acute treatment of migraine - In September 2024 , the Company initiated a Phase 2 study of an orally administered TRPM3 antagonist, BHV-2100, in the acute treatment of migraine. The study is a randomized, double-blind, placebo-controlled trial assessing the efficacy and safety of two doses (75 mg and 150 mg) of BHV-2100 in the acute treatment of migraine. The trial is designed to support registration with FDA-accepted co-primary endpoints of pain freedom and freedom from most bothersome symptom at 2 hours and is expected to enroll approximately 575 patients across 60 sites in the United States . Public offering - On October 2, 2024 , the Company closed its previously announced underwritten public offering of 6,052,631 of its common shares, which included the full exercise of the underwriters' option to purchase additional shares, at the public offering price of $47.50 per share. The net proceeds raised in the offering, after deducting underwriting discounts and estimated expenses of the offering payable by the Company, were approximately $269.9M . As of November 8, 2024 , we had 101,122,246 common shares outstanding. Expected Upcoming Milestones: We believe Biohaven is well positioned to achieve significant milestones in 2024 and 2025 across numerous programs: Selective Kv7 Activator: Continue 5 ongoing Phase 2/3 trials with BHV-7000 in focal epilepsy, idiopathic generalized epilepsy, MDD, and bipolar disorder Troriluzole: NDA submission to FDA on track for 4Q 2024, following release of pivotal topline results in SCA in September 2024 Two Phase 3 trials with troriluzole in OCD; expect to conduct interim analysis of the second Phase 3 OCD trial in 4Q 2024 and report topline data from first Phase 3 OCD trial in 1H 2025 Taldefgrobep alfa: Report topline data from Phase 3 trial with taldefgrobep in SMA in 4Q 2024 Initiate Phase 2 trial with taldefgrobep in obesity in 4Q 2024 or early 2025 First-in-class TRPM3 Antagonist: Continue advancing enrollment in Phase 2 trial with BHV-2100 in acute migraine and neuropathic pain (laser-evoked potential experimental pain paradigm) TYK2/JAK1 Inhibitor: Complete SAD/MAD studies with BHV-8000 and advance to Phase 2 in the coming months MoDE™ Platform Submit a total of 4 INDs in 2024 Continue to advance Phase 1 SAD and MAD studies with subcutaneous BHV-1300, with a further study update in 4Q 2024 Next Generation ADC Platform: Advance Phase 1 Trop-2 directed program BHV-1510 in multiple tumor types Capital Position: Cash, cash equivalents, marketable securities and restricted cash as of October 2, 2024 totaled approximately $642 million , which includes net proceeds of $269.9 million from the public offering of 6,052,631 common shares completed on October 2, 2024 . Third Quarter 2024 Financial Highlights: Research and Development (R&D) Expenses: R&D expenses, including non-cash share-based compensation costs, were $157.6 million for the three months ended September 30, 2024 , compared to $95.5 million for the three months ended September 30, 2023 . The increase of $62.1 million was due to additional and advancing clinical trials, including late Phase 3 and Phase 2/3 studies, and preclinical research programs in 2024, as compared to the same period in the prior year. Non-cash share-based compensation expense was $7.2 million for the three months ended September 30, 2024 , an increase of $5.0 million as compared to the same period in 2023. Non-cash share-based compensation expense was higher in the third quarter of 2024, primarily due to our annual equity incentive awards granted in the fourth quarter of 2023 and the first quarter of 2024. General and Administrative (G&A) Expenses: G&A expenses were $20.6 million for the three months ended September 30, 2024 , compared to $15.0 million for the three months ended September 30, 2023 . The increase of $5.5 million was partly due to increased non-cash share-based compensation expense, which was $5.0 million for the three months ended September 30, 2024 , an increase of $2.7 million as compared to the same period in 2023. Non-cash share-based compensation expense was higher in the third quarter of 2024 primarily due to our annual equity incentive awards granted in the fourth quarter of 2023 and the first quarter of 2024. Other Income, Net: Other income, net was $17.8 million for the three months ended September 30, 2024 , compared to other income, net of $4.7 million for the three months ended September 30, 2023 . The increase of $13.1 million was primarily due to non-cash changes in the fair value of our derivative liabilities recorded in connection with the amendment to our Membership Interest Purchase Agreement with Knopp Biosciences LLC in May 2024 (the Knopp Amendment), as well as increased investment income, partially offset by changes in the fair value of our forward contract liability recorded in connection with the Knopp Amendment. Net Loss: Biohaven reported a net loss for the three months ended September 30, 2024 of $160.3 million , or $1.70 per share, compared to $102.6 million , or $1.50 per share, for the same period in 2023. Non-GAAP adjusted net loss for the three months ended September 30, 2024 was $164.1 million , or $1.74 per share, compared to $98.1 million , or $1.44 per share for the same period in 2023. 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 losses from the change in fair value of derivatives. A reconciliation of the GAAP financial results to non-GAAP financial results is included in the tables below. Non-GAAP Financial MeasuresThis press release includes financial results prepared in accordance with accounting principles generally accepted in the United States (GAAP), and certain non-GAAP financial measures. In particular, Biohaven has provided non-GAAP adjusted net loss and adjusted net loss per share, which are adjusted to exclude non-cash share-based compensation, which is substantially dependent on changes in the market price of common shares, and changes in the fair value of derivative liabilities, which do not correlate to actual cash payment obligations in the relevant periods. 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 and can assist investors in comparing 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 news release. About Biohaven Biohaven is a biopharmaceutical company focused on the discovery, development, and commercialization of life-changing treatments in key therapeutic areas, including immunology, neuroscience, and oncology. The company is advancing its innovative portfolio of therapeutics, leveraging its proven drug development experience and multiple proprietary drug development platforms. Biohaven's extensive clinical and preclinical programs include Kv7 ion channel modulation for epilepsy and mood disorders; extracellular protein degradation for immunological diseases; TRPM3 antagonism for migraine and neuropathic pain; TYK2/JAK1 inhibition for neuroinflammatory disorders; glutamate modulation for OCD and SCA; myostatin inhibition for neuromuscular and metabolic diseases, including SMA and obesity; antibody recruiting bispecific molecules and antibody drug conjugates for cancer. Forward-looking StatementsThis news release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The use of certain words, including "continue", "plan", "will", "believe", "may", "expect", "anticipate" and similar expressions, is intended to identify forward-looking statements. Investors are cautioned that any forward-looking statements, including statements regarding the future development, timing and potential marketing approval and commercialization of development candidates, are not guarantees of future performance or results and involve substantial risks and uncertainties. Actual results, developments and events may differ materially from those in the forward-looking statements as a result of various factors including: the expected timing, commencement and outcomes of Biohaven's planned and ongoing clinical trials; the timing of planned interactions and filings with the FDA; the timing and outcome of expected regulatory filings; complying with applicable U.S. regulatory requirements; the potential commercialization of Biohaven's product candidates; the potential for Biohaven's product candidates to be first in class therapies; and the effectiveness and safety of Biohaven's product candidates. Additional important factors to be considered in connection with forward-looking statements are described in Biohaven's filings with the Securities and Exchange Commission , including within the sections titled "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations". The forward-looking statements are made as of the date of this news release, and Biohaven does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. BIOHAVEN LTD. CONSOLIDATED STATEMENTS OF OPERATIONS (Amounts in thousands, except share and per share amounts) (Unaudited) Three Months Ended September 30 , Nine Months Ended September30, 2024 2023 2024 2023 Operating expenses: Research and development $ 157,607 $ 95,517 $ 628,398 $ 238,468 General and administrative 20,561 15,030 66,782 43,872 Total operating expenses 178,168 110,547 695,180 282,340 Loss from operations (178,168) (110,547) (695,180) (282,340) Other income, net 17,805 4,686 36,288 18,757 Loss before (benefit) provision for income taxes (160,363) (105,861) (658,892) (263,583) (Benefit) provision for income taxes (59) (3,287) 687 (171) Net loss $ (160,304) $ (102,574) $ (659,579) $ (263,412) Net loss per share — basic and diluted $ (1.70) $ (1.50) $ (7.50) $ (3.86) Weighted average common shares outstanding— basic and diluted 94,372,159 68,320,125 87,936,923 68,258,757 BIOHAVEN LTD. CONSOLIDATED BALANCE SHEETS (Amounts in thousands, except share amounts) September 30, 2024 December 31, 2023 (Unaudited) Assets Current assets: Cash and cash equivalents $ 84,390 $ 248,402 Marketable securities 294,426 133,417 Prepaid expenses 55,168 35,242 Income tax receivable 5,318 13,252 Other current assets 1,198 12,133 Total current assets 440,500 442,446 Property and equipment, net 18,276 17,191 Intangible assets 18,400 18,400 Goodwill 1,390 1,390 Other non-current assets 31,957 33,785 Total assets $ 510,523 $ 513,212 Liabilities and Shareholders' Equity Current liabilities: Accounts payable $ 19,744 $ 15,577 Accrued expenses and other current liabilities 63,520 39,846 Forward contract liability 69,030 — Total current liabilities 152,294 55,423 Non-current operating lease liabilities 25,312 27,569 Derivative liability, non-current 12,320 — Other non-current liabilities 4,591 2,245 Total liabilities 194,517 85,237 Shareholders' Equity: Preferred shares, no par value; 10,000,000 shares authorized, no shares issuedand outstanding as of September 30, 2024 and December 31, 2023 — — Common shares, no par value; 200,000,000 shares authorized as of September30, 2024 and December 31, 2023 ; 94,899,193 and 81,115,723 shares issuedand outstanding as of September 30, 2024 and December 31, 2023 ,respectively 1,381,699 887,528 Additional paid-in capital 93,038 39,804 Accumulated deficit (1,158,871) (499,292) Accumulated other comprehensive income (loss) 140 (65) Total shareholders' equity 316,006 427,975 Total liabilities and shareholders' equity $ 510,523 $ 513,212 BIOHAVEN LTD. RECONCILIATION OF GAAP TO NON-GAAP FINANCIAL MEASURES (Amounts in thousands, except share and per share amounts) (Unaudited) Three Months Ended September 30 , Nine Months Ended September30, 2024 2023 2024 2023 Reconciliation of GAAP to Non-GAAP adjusted net loss: GAAP net loss $ (160,304) $ (102,574) $ (659,579) $ (263,412) Add: non-cash share-based compensation expense 12,160 4,456 59,269 12,916 Add: (gain) loss from change in fair value of derivatives (15,990) — (17,030) — Non-GAAP adjusted net loss $ (164,134) $ (98,118) $ (617,340) $ (250,496) Reconciliation of GAAP to Non-GAAP adjusted net loss per share — basic and diluted: GAAP net loss per share — basic and diluted $ (1.70) $ (1.50) $ (7.50) $ (3.86) Add: non-cash share-based compensation expense 0.13 0.07 0.67 0.20 Add: (gain) loss from change in fair value of derivatives (0.17) — (0.19) — Non-GAAP adjusted net loss per share — basic and diluted $ (1.74) $ (1.44) $ (7.02) $ (3.67) MoDEs is a trademark of Biohaven Therapeutics Ltd. Libtayo is a registered trademark of Regeneron Pharmaceuticals, Inc. Investor Contact: Jennifer Porcelli Vice President, Investor Relationsjennifer.porcelli@biohavenpharma.com+1 (201) 248-0741 Media Contact: Mike Beyer Sam Brown Inc. mikebeyer@sambrown.com+1 (312) 961-2502 View original content to download multimedia:https://www.prnewswire.com/news-releases/biohaven-reports-third-quarter-2024-financial-results-and-recent-business-developments-302303249.html SOURCE Biohaven Ltd.

Cash, cash equivalents, marketable securities and restricted cash totaled approximately $440 million on June 30, 2024 Biohaven's Molecular Degrader of Extracellular Proteins (MoDE™) platform advancing multiple new targets and reported positive interim data from its lead investigational drug in an ongoing Phase 1 study of BHV-1300: The Company reported dose-dependent and rapid IgG reductions in its ongoing Phase 1 trial with its lead investigational degrader BHV-1300 No serious adverse events (SAEs) reported with BHV-1300 to date; most adverse events (AEs) were mild, deemed unrelated to study drug and resolved spontaneously Phase 1 study also completed an assessment of an optimized subcutaneous (SC) formulation of BHV-1300 that demonstrated approximately a 44% higher than expected exposure compared to the dose-equivalent intravenous formulation previously studied; this new human data further confirms feasibility of convenient self-administered SC auto-injector and the SC formulation was not associated with injection site reactions Degrader platform expected to deliver 3 INDs for new MoDE programs before year-end in addition to continued data from SAD/MAD with BHV-1300 Biohaven's beta-1 adrenergic receptor (β1AR) autoantibody targeting MoDE, BHV-1600, granted INTERACT meeting with FDA in 2H 2024 regarding development program for dilated cardiomyopathy Advancing novel ion channel program targeting Kv7 activation and TRPM3 antagonism across multiple neurological, pain and neuropsychiatric disease indications: 5 Phase 2/3 trials with BHV-7000 underway in epilepsy and mood disorders Released positive Phase 1 data with TRPM3 antagonist BHV-2100 showing drug concentrations above EC90 target and well-tolerated profile across all doses in SAD/MAD study; advancing Phase 2 study in acute migraine and proof-of-concept (POC) study in pain in 2H 2024 Taldefgrobep alfa, a myostatin-inhibitor, progressing on track with Phase 3 topline data in spinal muscular atrophy (SMA) and Phase 2 trial initiation in obesity expected in 2H 2024 Taldefgrobep alfa has demonstrated direct effects on reducing adipose tissue (including lipid storage and mitochondrial content) independent of increases in muscle mass In a MAD study, conducted in healthy adults, taldefgrobep alfa (45 mg SC QW) produced significant reductions in total body fat while increasing total body lean mass Preclinical data released at the 2024 American Diabetes Association conference demonstrated that taldefgrobep alfa, as a monotherapy or in combination with a GLP-1 agonist, demonstrated significant reductions in fat and total body weight. Taldefgrobep alfa-treated animals showed significant increases in lean muscle, despite co-administration with a GLP-1 receptor agonist Tyrosine Kinase 2/Janus Kinase 1 (TYK2/JAK1) selective inhibitor, BHV-8000, completed Phase 1 and confirmed biomarker target engagement with reductions in inflammatory markers and demonstrated central nervous system penetration with confirmed cerebrospinal fluid (CSF) target exposures in healthy subjects Advancing registrational programs for Parkinson's disease and prevention of Amyloid-Related Imaging Abnormalities (ARIA) following interactions with the FDA Expect interim data analysis from second ongoing Phase 3 OCD trial with troriluzole in 2H 2024; topline data from first Phase 3 OCD trial expected in 1H 2025 SCA interactions with troriluzole filing in Europe ongoing and constructive interactions in the US with the FDA New real-world evidence (RWE) protocol, incorporating feedback from the FDA, assessing 3-years of treatment with troriluzole expected to deliver topline results in 2H 2024 Biohaven antibody drug conjugate (ADC) portfolio positioned to deliver differentiated profiles and address unmet needs in oncology: BHV-1510 currently dosing cancer patients in Phase1/2 study and now advancing towards combination with Libtayo® by 4Q 2024 Portfolio of multiple advanced nonclinical BHVN ADCs demonstrate improved plasma stability and in vitro/in vivo differentiation NEW HAVEN, Conn., Aug. 8, 2024 /PRNewswire/ -- 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 to treat a broad range of rare and common diseases, today reported financial results for the second quarter ended June 30, 2024, and provided a review of recent accomplishments and anticipated upcoming developments. Vlad Coric, M.D., Chairman and Chief Executive Officer of Biohaven, commented, "Last quarter, we showcased an array of exciting updates across our pipeline spanning immunology, neuroscience, obesity, and oncology at our annual R&D Day. First, it has been incredible working with Yale Professor David Spiegel and my colleagues at Biohaven to drive the advancement of groundbreaking degrader science represented by BHV-1300 using our Molecular Degrader of Extracellular Protein (MoDE™) technology — we consider our initial Phase 1 data to be paradigm-shifting and we are accelerating our entire platform based upon these early results. BHV-1300 has been well-tolerated with no significant adverse effects and no clinically significant lab abnormalities or ECG changes observed to date and emerging subcutaneous data from our Phase 1 study highlights the ease of use of this technology. The platform represents a brand-new technology that has potential to treat diseases like Type 1 diabetes, autoimmune dilated cardiomyopathy, IgA nephropathy, and many others. Our differentiation continues to focus on convenient SC patient self-administration, rapid onset of action, potential for deeper IgG reduction and concurrent use with Fc containing standard of care biologics. We are excited that we remain on timelines with multiple INDs from our MoDE platform for later this year, including drug candidates that target autoantibodies against β-1AR for the potential treatment of dilated cardiomyopathy, galactose deficient IgA for IgA nephropathy and a further optimized IgG degrader for use in rare diseases." Dr. Coric continued, "While our degrader program continues to garner significant focus, our broader pipeline is increasingly derisked with several potentially paradigm-shifting treatments for conditions including epilepsy, mood disorders, pain, immunology, rare diseases, obesity and neurodegenerative disorders. Starting with our ion channel platform; five studies with Kv7 activator BHV-7000 (three in epilepsy and two in major depressive disorder and bipolar) are underway with brisk patient enrollment. In addition, our TRPM3 antagonist BHV-2100 has completed its initial Phase 1 SAD/MAD study, attaining an exceptional PK/PD profile for the treatment of migraine and other pain disorders. All doses being advanced have reached the targeted EC90 for this molecule with excellent preliminary safety. We are excited about being back in the migraine space with this novel target and will initiate a Phase 2 study in migraine before year end, as well as initiate a POC study as a non-opiate pain treatment. With BHV-8000, our oral and brain penetrant TYK2/JAK1 inhibitor, we have aligned with the FDA on two novel study designs: one for the prevention of ARIA associated with amyloid lowering agents in Alzheimer's disease and another with the goal of slowing disease progression in early Parkinson's disease. The Phase 1 profile of BHV-8000 is invigorating our translational team as we have data confirming both CNS penetration and biomarker engagement of inflammatory targets in humans. Regarding our anti-myostatin taldefgrobep alfa, we shared new preclinical data demonstrating improved, durable weight reduction and lean mass preservation in combo with GLP-1 semaglutide, which was particularly noteworthy, given the muscle wasting limitations that have plagued the GLP-1 class. We also showed that taldefgrobep has direct effects on modulating fat in addition to increasing muscle mass. Our oncology platform has also emerged into the clinic with our lead Trop-2 ADC, BHV-1510, enrolling cancer patients and our efforts advancing a portfolio of several Biohaven ADCs. We are excited to get preliminary safety and efficacy data from cancer patients suffering with select advanced or metastatic epithelial tumors in the Phase 1/2 study of BHV-1510 and will be evaluating the combination of BHV-1510 with Regeneron's anti-PD1 Libtayo — combination dosing with BHV-1510 and Libtayo is anticipated to begin in 2H 2024. Finally, with our glutamate platform represented by troriluzole, topline data from an interim analysis of the second OCD trial is expected in 2H 2024 and our first OCD trial is expected to read out in 1H 2025. Separately, we continue to have constructive dialogue with the FDA regarding our SCA development program and our European Medicines Agency application for SCA3 remains under review. We now expect topline data from a new RWE protocol assessing the efficacy of troriluzole in SCA patients treated for up to 3 years— this includes new patient data that has not previously been available. I never cease to be amazed by the power of our small but mighty Biohaven R&D team that has innovated across each of these important medical areas. We are driven to fulfill a promise to patients and our investors that we will diligently evaluate and advance potentially transformative therapies to those suffering from disease." Second Quarter 2024 and Recent Business Highlights Additional data supports the paradigm-shifting potential of the MoDE Platform for the treatment of immunological and inflammatory disorders – In May 2024, the Company disclosed positive new data from its ongoing Phase 1 SAD study in healthy subjects with BHV-1300, a first-in-human IgG degrader from its innovative MoDE platform. Results from the initial dose cohorts in the SAD study confirmed that BHV-1300 rapidly and selectively lowers IgG in a dose-dependent manner. Emerging Phase 1 data also showed that our novel SC formulation of BHV-1300 delivered exposures higher than the intravenous formulation, enabling the profile of a convenient patient administered auto-injector to attain targeted reduction of IgG. The Company expects to provide an update from our SAD and MAD studies of BHV-1300 in the second half of 2024 and is on schedule to file multiple new MoDE INDs this year. FDA granted INTERACT meeting request for BHV-1600, β1AR autoantibody MoDE, development program. Ion Channel Platform: Kv7 activator and TRPM3 antagonist candidates represent transformational targets in neurology and neuropsychiatry – The Company is enrolling participants in five ongoing pivotal clinical trials with Kv7 activator, BHV-7000, targeting focal epilepsy, generalized epilepsy, bipolar disorder and major depressive disorder; separately, Phase 2 and POC studies are planned in migraine and pain, respectively, with the TRPM3 antagonist, BHV-2100, in 2H 2024. Committed to improving muscle health with Myostatin Platform – In May 2024, the Company presented new preclinical data showing that administration of taldefgrobep alfa directly reduced the increased adipose fat storage caused by myostatin; the Company also presented new preclinical data from a diet-induced obesity mouse model showing treatment with taldefgrobep alfa together with a GLP-1 agonist produced greater reductions in body weight and fat mass, and a larger increase in lean muscle mass, compared to treatment with GLP-1 alone. The Company plans to initiate a Phase 2 study in obesity in 2H2024. Separately, the Company continues to expect Phase 3 study topline results in SMA in 2H 2024. Selectively targeting the immune system to treat neurodegenerative diseases with neuroinflammation platform – In May 2024, the Company reported positive results from the Phase 1 SAD and MAD study with our brain-penetrant TYK2/JAK1 inhibitor, BHV-8000 in healthy subjects, including demonstration of CSF target exposures and biomarker engagement along with a well-tolerated safety profile. The Company also announced key regulatory updates, including the successful completion of two FDA meetings with favorable feedback enabling registrational programs for Parkinson's disease and for the prevention of ARIA, a novel indication. Oncology Platform: Antibody Drug Conjugate portfolio: positioned to achieve enhanced stability and improved efficacy – In May 2024, the Company announced that its novel Trop-2 ADC, BHV-1510, entered into the clinic for patients with advanced or metastatic epithelial tumors; the first patient was dosed in a Phase 1/2 clinical trial as monotherapy. Biohaven also entered into a clinical supply agreement with Regeneron to study the combination of BHV-1510 with Regeneron's anti-PD1 Libtayo (cemiplimab-rwlc) in the clinical study. Expected Upcoming Milestones: We believe Biohaven is well positioned to achieve significant milestones in 2024 and 2025 across numerous programs: Selective Kv7 Activator: Continue 5 ongoing Phase 2/3 trials with BHV-7000 in focal epilepsy, idiopathic generalized epilepsy, MDD, and bipolar disorder Troriluzole: Topline results from a new RWE protocol of 3-year data from troriluzole treated patients in SCA in 2H 2024 Two Phase 3 trials with troriluzole in OCD: conduct interim analysis of the second Phase 3 OCD trial in 2H 2024 and report topline data from first Phase 3 OCD trial in 1H 2025 Taldefgrobep alfa: Initiate Phase 2 trial with taldefgrobep in obesity in 2H 2024 Report topline data from Phase 3 trial with taldefgrobep in SMA in 2H 2024 First-in-class TRPM3 Antagonist: Initiate Phase 2 trial with BHV-2100 in acute migraine in 2H 2024 Initiate POC study with BHV-2100 for pain in 2H 2024 TYK2/JAK1 Inhibitor: Complete SAD/MAD studies with BHV-8000 and advance to Phase 2 in the coming months MoDE™ Platform Submit a total of 4 INDs in 2024 Continue to advance Phase 1 SAD and MAD studies with BHV-1300, with a further study update in 2H 2024 INTERACT meeting with FDA regarding BHV-1600, β1AR autoantibody degrader, in 2H 2024 Next Generation ADC Platform: Advance Phase 1 Trop-2 directed program BHV-1510 into a Phase 1 study in multiple tumor types Capital Position: Cash, cash equivalents, marketable securities and restricted cash totaled approximately $440 million on June 30, 2024. Second Quarter 2024 Financial Highlights: Research and Development (R&D) Expenses: R&D expenses, including non-cash share-based compensation costs, were $314.8 million for the three months ended June 30, 2024, compared to $79.5 million for the three months ended June 30, 2023. The increase was primarily due to a one-time, non-cash expense of $171.9 million paid to Knopp Biosciences, LLC (Knopp) for a milestone and royalty buyback related to our BHV-7000 and broader Kv7 platform that was recognized during the three months ended June 30, 2024 (the buyback reduced our potential future milestone payments by $867.5 million, and replaced the scaled high single digit to low teens royalty payment obligations with a flat royalty payment in the mid-single digits for the Kv7 programs). The increase in R&D expenses was also due to advancing our 6 clinical platforms including 5 Phase 3 starts for BHV-7000, follow-on Kv7 assets, preclinical research programs, and increases in direct program spend for additional and advancing multiple clinical development programs. Non-cash share-based compensation expense was $7.1 million for the three months ended June 30, 2024, an increase of $4.6 million as compared to the same period in 2023. Non-cash share-based compensation expense was higher in the second quarter of 2024, primarily due to our annual equity incentive awards granted in the fourth quarter of 2023 and the first quarter of 2024. General and Administrative (G&A) Expenses: General and administrative expenses were $19.0 million for the three months ended June 30, 2024, compared to $14.5 million for the three months ended June 30, 2023. The increase of $4.4 million was primarily due to increased non-cash share-based compensation expense, which was $5.2 million for the three months ended June 30, 2024, an increase of $2.9 million as compared to the same period in 2023. Non-cash share-based compensation expense was higher in the second quarter of 2024 primarily due to our annual equity incentive awards granted in the fourth quarter of 2023 and the first quarter of 2024. Other Income, Net: Other income, net was a net other income of $14.2 million for the three months ended June 30, 2024, compared to a net other income of $5.8 million for the three months ended June 30, 2023. The increase of $8.3 million was primarily due to a $9.2 million gain recorded upon the settlement of our forward contract liability for share consideration issued under the amendment entered into with Knopp in May 2024, and increased investment income, partially offset by a decrease in other income recognized during the three months ended June 30, 2024, as compared to the same period in 2023 related to the Transition Services Agreement entered into with Biohaven Pharmaceutical Holding Company Ltd. (the Former Parent). Net Loss: Biohaven reported a net loss for the three months ended June 30, 2024 of $319.8 million, or $3.64 per share, compared to $90.3 million, or $1.32 per share, for the same period in 2023. Non-GAAP adjusted net loss for the three months ended June 30, 2024 was $307.4 million, or $3.50 per share, compared to $85.7 million, or $1.25 per share for the same period in 2023. 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 losses from the change in fair value of derivatives. 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 certain non-GAAP financial measures. In particular, Biohaven has provided non-GAAP adjusted net loss and adjusted net loss per share, which are adjusted to exclude non-cash share-based compensation, which is substantially dependent on changes in the market price of common shares, and changes in the fair value of derivative liabilities, which do not correlate to actual cash payment obligations in the relevant periods. 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 and can assist investors in comparing 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 news release. About Biohaven Biohaven is a biopharmaceutical company focused on the discovery, development, and commercialization of life-changing treatments in key therapeutic areas, including immunology, neuroscience, and oncology. The company is advancing its innovative portfolio of therapeutics, leveraging its proven drug development experience and multiple proprietary drug development platforms. Biohaven's extensive clinical and preclinical programs include Kv7 ion channel modulation for epilepsy and mood disorders; extracellular protein degradation for immunological diseases; TRPM3 antagonism for migraine and neuropathic pain; TYK2/JAK1 inhibition for neuroinflammatory disorders; glutamate modulation for OCD and SCA (spinocerebellar ataxia); myostatin inhibition for neuromuscular and metabolic diseases, including SMA and obesity; antibody recruiting bispecific molecules and antibody drug conjugates for cancer. Forward-looking Statements This news release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The use of certain words, including "continue", "plan", "will", "believe", "may", "expect", "anticipate" and similar expressions, is intended to identify forward-looking statements. Investors are cautioned that any forward-looking statements, including statements regarding the future development, timing and potential marketing approval and commercialization of development candidates, are not guarantees of future performance or results and involve substantial risks and uncertainties. Actual results, developments and events may differ materially from those in the forward-looking statements as a result of various factors including: the expected timing, commencement and outcomes of Biohaven's planned and ongoing clinical trials; the timing of planned interactions and filings with the FDA; the timing and outcome of expected regulatory filings; complying with applicable U.S. regulatory requirements; the potential commercialization of Biohaven's product candidates; the potential for Biohaven's product candidates to be first in class therapies; and the effectiveness and safety of Biohaven's product candidates. Additional important factors to be considered in connection with forward-looking statements are described in Biohaven's filings with the Securities and Exchange Commission, including within the sections titled "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations". The forward-looking statements are made as of the date of this news release, and Biohaven does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. MoDEs is a trademark of Biohaven Therapeutics Ltd. Libtayo is a registered trademark of Regeneron Pharmaceuticals, Inc. Investor Contact: Jennifer Porcelli Vice President, Investor Relations [email protected] +1 (201) 248-0741 Media Contact: Mike Beyer Sam Brown Inc. [email protected] +1 (312) 961-2502 SOURCE Biohaven Ltd.

One concern about the GLP-1 class of metabolic disorder drugs is that the weight patients lose includes muscle as well as fat. BioAge Labs wants to test whether its experimental medication, dosed alongside Eli Lilly’s weight management drug Zepbound, can preserve muscle mass. The startup recently closed $170 million to finance a mid-stage clinical trial. BioAge develops drugs that address aspects of human aging. Its lead drug candidate, azelaprag, is a small molecule designed to bind to and activate the apelin receptor, which regulates muscle metabolism, growth, and repair. This drug came from the labs of Amgen, which initially developed it for treating heart failure. Amgen’s Phase 1 tests showed the drug hit its target with a clean safety profile, BioAge CEO Kristen Fortney told MedCity News in a 2022 interview. But as a heart drug, the results were “not dramatic,” she said. Amgen elected to shelve the molecule. Richmond, California-based BioAge licensed it from the pharma giant in 2021, with the goal of testing it as a way of preserving muscle mass in elderly people. In BioAge’s Phase 1b study enrolling 21 participants age 65 and older, results showed the experimental drug led to statistically significant prevention of muscle atrophy relative to a placebo after 10 days of bed rest. The company planned to proceed to larger Phase 2 test enrolling intensive care unit patients, who can lose more than 15% of their muscle mass in just one week, according to published research. Last fall, BioAge announced the Phase 2 trial would go in a different direction. Instead of testing azelaprag in ICU patients, the trial will evaluate the drug alongside Eli Lilly’s Zepbound. The injectable drug, which activates the GLP-1 and GIP receptors, is an incretin mimetic, a type of drug that works by mimicking hormones found in the gut. The new clinical trial plan is based on preclinical research in obese mice. Results reported last year showed that treating the mice with both azelaprag and Lilly’s drug led to greater weight loss than what was achieved with the Lilly drug alone. The drug pairing also led to improvement in body composition and muscle function. Under a collaboration agreement, Lilly will supply Zepbound for BioAge’s trial, which will be run in collaboration with Chorus, a small independent clinical development organization within the pharma giant. BioAge adjusted its focus for azelaprag after the company’s technology uncovered new insight about the molecule. The BioAge discovery platform, built on analysis of human longevity data, identified a link between the apelin pathway activity and physical function during aging, Fortney said in an email. While the Phase 1b clinical trial led to results showing significant muscle and metabolic benefits in healthy elderly volunteers on bed rest, the molecule’s mechanism has multiple potential applications, Fortney said. “Obesity is the indication we are focusing on given the strong weight loss synergy we see preclinically with incretins,” she said. “This is an oral drug with the potential to increase weight loss quantity with a fully oral regimen, as well as to improve weight loss quality.” Fortney said BioAge will share more details on the design of the Phase 2 trial in the future, but the study will compare azelaprag (known at BioAge as BGE-105) in combination with Zepbound versus Zepbound alone. The primary endpoint will be weight loss. In addition, the company will monitor exploratory endpoints related to improvement of body composition—the balance of lean mass to fat mass. BioAge’s new capital will finance the planned Phase 2 test, which is on track to start in mid-2024. The Series D round was led by Sofinnova Investments. New investors joining the financing include Longitude Capital, RA Capital Management, Cormorant Asset Management, RTW Investments, SV Health Investors, OrbiMed Advisors, Sands Capital, Pivotal bioVenture Partners, Osage University Partners, Lilly Ventures, and Amgen Ventures. The latest round also included participation from earlier investor Andreessen Horowitz. Here’s a look at other recent life science industry financing activity: —Frontier Medicines, developer of targeted medicines for oncology and immunology, closed $80 million in financing to support its pipeline. The biotech’s most advanced program is FMC-376, which is in development for treating patients whose cancer is positive for KRAS G12C. This mutation was first drugged by Lumakras from Amgen and then Krazati from Mirati Therapeutics. Both drugs lock KRAS G12C protein in an inactive state. Frontier’s drug candidate is designed to block this cancer-driving protein in either its active or inactive states, potentially offering an option for patients who have not responded to the Amgen or Mirati drugs. In addition to supporting FMC-376, which recently dosed the first patient in a Phase 1/2 study, Frontier said the new capital will support other wholly owned programs in its pipeline. Deerfield Management Company and Droia Venture co-led the company’s Series C financing, which also included “significant participation” by Belgium-based drugmaker Galapagos. Frontier last raised money in 2021, an $88.5 million Series B round. —Firefly Bio revealed $94 million to finance R&D of degrader antibody conjugates, or DACs, which carry a protein degrader as the drug payload. In preclinical research, the biotech said its drugs led to “significant reduction of tumor volume at very low doses.” Firefly was incubated by Versant Ventures, which co-led the startup’s Series A financing with MPM BioImpact. —Roche, already an investor in liquid biopsy company Freenome, led an additional $254 million financing for the company. South San Francisco-based Freenome will apply the cash toward ongoing pivotal clinical trials evaluating its blood screening technology in colorectal cancer and lung cancer. The company is also conducting a study of its technology as a way to detect multiple cancers. Roche last invested in Freenome two years ago, a $290 million infusion that followed the company’s $300 million Series D financing. —Latigo Biotherapeutics launched with $135 million to finance clinical development of a non-opioid drug that blocks NaV1.8, a sodium channel associated with pain. It’s the same target addressed by a Vertex Pharmaceuticals drug candidate that recently posted data showing it met its main Phase 3 goal assessing pain relief compared to a placebo. But on a secondary goal of showing superiority to standard of care Vicodin, the Vertex drug came up short. Thousand Oaks, California-based Latigo claims its drug could be best in the class of NaV1.8 inhibitors with rapid onset, meaningful efficacy, and superior safety. It’s currently in Phase 1 testing. Latigo’s Series A financing was led by Westlake Village BioPartners, which incubated the startup. —Cancer immunotherapy developer NextPoint Therapeutics added $42.5 million to its Series B financing, bringing the round’s total to $122.5 million. The drugs of Cambridge, Massachusetts-based NextPoint target the HHLA2 pathway. NextPoint first announced its Series B round last year. —Sudo Biosciences expanded its Series B financing by $31 million, bringing the round’s total to $147 million. The new investors are Dementia Discovery Fund, Leaps by Bayer, and UPMC Enterprises. Carmel, Indiana-based Sudo emerged from stealth in 2022 to develop small molecule drugs that address TYK2, an autoimmune disease target first hit by the Bristol Myers Squibb drug Sotyktu. —Alys Pharmaceuticals launched with $100 million from Medicxi, the investment firm that formed the company. The preclinical biotech, which focuses on developing treatments for immune disorders of the skin, was formed by combining six Medicxi portfolio companies. Target indications include atopic dermatitis, vitiligo, psoriasis, and mastocytosis. —Antibody drug conjugate developer ProfoundBio closed $112 million in financing, which will be applied to clinical development of its pipeline. Lead program rinatbart sesuctecan, or Rina-S, targets folate receptor alpha, a validated cancer target. A pivotal Phase 1/2 study is underway in ovarian cancer. Ally Bridge Group led the Seattle-based biotech’s Series B round. ProfoundBio, whose management team brings experience from ADC specialist Seagen, emerged in 2021 backed by a $55 million Series A financing. —Areteia Therapeutics expanded its Series A round by $75 million with the addition of new investors Viking Global Investors and Marshall Wace. The Chapel Hill, North Carolina-based biotech’s Series A financing was announced at $350 million in 2022. Lead drug candidate dexpramipexole comes from the labs of Knopp Biosciences. Areteia is currently testing the molecule in three Phase 3 clinical trials enrolling patients with eosinophilic asthma, a severe form of asthma. —Basking Biosciences raised $55 million in a financing led by Arch Venture Partners. Columbus, Ohio-based Basking will use the capital to continue clinical development of BB-031, a potential treatment for acute ischemic stroke. The Basking drug is a reversible RNA aptamer designed to target von Willebrand factor, a clotting protein. BB-031 is engineered for both rapid onset and short duration of effect. Basking plans to start Phase 2 testing later this year. —Neurona Therapeutics, developer of regenerative medicines for neurological disorders, closed $120 million in financing. The San Francisco-based biotech makes cell therapies from human pluripotent stem cells, which have the ability to become almost any type of cell. Neurona will apply the capital toward ongoing Phase 1/2 testing of NRTX-1001, developed as a one-time treatment to silence epileptic seizures. Viking Global Investors and Cormorant Asset Management co-led Neurona’s Series E round. —Cour Pharmaceuticals has already out-licensed a celiac disease therapeutic candidate to Takeda Pharmaceuticals, which has advanced the nanoparticle-based therapy to Phase 2 testing. Chicago-based Cour wants to develop its own drug candidates and it raised $105 million to support programs in type 1 diabetes and myasthenia gravis. Lumira Ventures and Alpha Wave Ventures co-led the Series A financing, which included participation from three big pharma companies. —Eyconis, a new company formed with assets from Ascendis Pharma, launched with a $150 million financing commitment from an investor syndicate that includes Frazier Life Sciences, RA Capital Management, venBio, and HealthQuest Capital. Eyconis, which will operate from Redwood City, California, has ophthalmology assets developed from Ascendis’s Transcon platform. Ascendis, which has an equity stake in Eyconis, granted the biotech rights to develop and commercialize Transcon ophthalmology products globally. —Synnovation Therapeutics, founded and led by veterans of Incyte, launched with $102 million for small molecule drugs addressing validated cancer targets. Lead program SNV1521 is a PARP1 inhibitor that is highly selective to that target and also has the ability to penetrate into the central nervous system. The Wilmington, Delaware-based company is testing this molecule in a Phase 1 clinical trial. Third Rock Ventures led Synnovation’s Series A financing, which included participation from Nextech, Lilly Asia Ventures, Sirona Capital, and Cormorant Asset Management. Photo by Eli Lilly