On August 7, 2024 SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a commercial-stage biopharmaceutical company focused on severe rare diseases and cancer, reported financial results for the second quarter of 2024 and provided an update on recent company developments (Press release, SpringWorks Therapeutics, AUG 7, 2024, View Source [SID1234645503]).

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"We are very pleased with the continued strong momentum of our U.S. launch of OGSIVEO for adults with desmoid tumors. In the second quarter, we also completed the submission of our NDA for mirdametinib in NF1-PN, which positions us to potentially have our second medicine available for patients in 2025," said Saqib Islam, Chief Executive Officer of SpringWorks. "Our focus for the second half of 2024 will be to drive broader adoption of OGSIVEO, to advance our commercial preparations for the launch of mirdametinib for children and adults with NF1-PN, to continue advancing OGSIVEO and mirdametinib through the European regulatory process, and to progress our emerging portfolio for patient populations with high unmet needs."

Recent Business Highlights and Upcoming Milestones

OGSIVEO (Nirogacestat)

Strong commercial execution of the OGSIVEO launch, with net product revenue of $40.2 million in the second quarter of 2024.
In May 2024, SpringWorks introduced OGSIVEO 150 mg and 100 mg tablets in blister packaging, which was developed to enhance patient convenience with OGSIVEO.
A Marketing Authorization Application (MAA) for nirogacestat for the treatment of adult patients with desmoid tumors is under review with the European Medicines Agency (EMA).
Additional data from the Phase 3 DeFi trial of nirogacestat in adults with desmoid tumors highlighting consistent safety and efficacy across subgroups of high-risk patient populations and updated ovarian toxicity resolution data supporting the transience of ovarian toxicity were presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.
SpringWorks expects to present long-term follow-up data from the Phase 3 DeFi trial at a medical conference in the second half of 2024.
SpringWorks expects to report initial data from the Phase 2 trial evaluating nirogacestat as a monotherapy in patients with recurrent ovarian granulosa cell tumors in the second half of 2024.
SpringWorks is continuing to support several industry and academic collaborator studies evaluating nirogacestat as part of B-cell maturation antigen (BCMA) combination therapy regimens across treatment lines in patients with multiple myeloma.
Mirdametinib

SpringWorks completed the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for mirdametinib for the treatment of children and adults with NF1-PN.
The Company expects to complete the submission of an MAA for mirdametinib for the treatment of children and adults with NF1-PN in the European Union in the second half of 2024.
Data from the pediatric and adult cohorts of the Phase 2b ReNeu trial were presented in an oral presentation at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting and were also featured at the 2024 Global NF Conference and at the International Symposium on Pediatric Neuro-Oncology (ISPNO) 2024 meeting. Results showed robust objective response rates confirmed by blinded independent central review, deep responses, significant reductions in pain, improvement in other quality of life measures, and a manageable and tolerable safety profile were achieved across both the pediatric and adult cohorts. SpringWorks expects to publish the ReNeu trial results in a peer-reviewed journal in the second half of 2024.
A poster evaluating the dispersible tablet of mirdametinib in children with NF1-PN in the ReNeu trial was presented at the ISPNO 2024 meeting. Patients and caregivers reported high acceptability scores for ease of swallowing and willingness to take the dispersible tablet formulation, indicating that this formulation provides an acceptable option for children or adults with swallowing difficulties.
Initial data from the Phase 1/2 trial evaluating mirdametinib in patients with pediatric low-grade gliomas (pLGG) were presented at the ISPNO 2024 meeting. Results from 23 patients enrolled in the Phase 1 portion of the study suggested that mirdametinib, which has high blood brain barrier penetration, has encouraging clinical activity in patients with recurrent/progressive pLGG across a variety of MAPK pathway aberrations. The Phase 2 portion of the study is ongoing and recruiting patients.
Emerging Pipeline

A Phase 1b trial evaluating brimarafenib (BGB-3245) in adult patients with RAF mutant solid tumors is ongoing; additional data from the dose expansion portion of the study is expected to be presented in the first half of 2025. Brimarafenib is an investigational, selective RAF dimer inhibitor being developed by MapKure, LLC, a joint venture between SpringWorks and BeiGene, Ltd.
Patients continue to be enrolled in several combination therapy oncology programs: a Phase 1/2a study of brimarafenib and mirdametinib in MAPK mutant solid tumors, a Phase 1b trial of brimarafenib and Amgen’s EGFR inhibitor, panitumumab, in colorectal and pancreatic cancer patients with known MAPK pathway mutations, and a Phase 1b trial of mirdametinib with BeiGene’s RAF dimer inhibitor, lifirafenib, in adult patients with NRAS mutant solid tumors.
SpringWorks initiated a Phase 1a trial of SW-682, an investigational novel, oral, potent, and selective pan-TEAD inhibitor, in Hippo-mutant solid tumors in the second quarter of 2024.
General Corporate

In July, SpringWorks appointed Martin Mackay, Ph.D. to the Company’s Board of Directors. Dr. Mackay is a highly accomplished R&D executive with more than 30 years of pharmaceutical and biotech R&D experience, including leadership roles at Pfizer, AstraZeneca and Alexion.
Second Quarter 2024 Financial Results

Product Revenue: OGSIVEO net product revenue was $40.2 million in the second quarter of 2024.
Selling, General and Administrative (SG&A) Expenses: SG&A expenses were $57.8 million for the second quarter of 2024, compared to $47.0 million for the comparable period of 2023. The increase in SG&A expense was primarily attributable to commercial activities supporting the U.S. launch of OGSIVEO, as well as commercial readiness activities to support the U.S. launch of mirdametinib, if approved.
Research and Development (R&D) Expenses: R&D expenses were $44.4 million for the second quarter of 2024, compared to $35.9 million for the comparable period of 2023. The increase in R&D expenses was primarily attributable to an increase in costs related to drug manufacturing, clinical trials, other research, consulting and professional services, and an increase in employee costs associated with headcount growth.
Net Loss Attributable to Common Stockholders: SpringWorks reported a net loss of $39.9 million, or $0.54 per share, for the second quarter of 2024. This compares to a net loss of $77.9 million, or $1.25 per share, for the comparable period of 2023.
Cash, Cash Equivalents, and Marketable Securities: Cash, cash equivalents and marketable securities were $521.9 million as of June 30, 2024.
Conference Call Information

SpringWorks will host a conference call and webcast today, Wednesday, August 7, at 8:30 a.m. ET to review its second quarter 2024 financial results and discuss recent business updates. To join the live webcast and view the corresponding slides, please click here. To access the live call by phone, please pre-register for the call by clicking here. Once registration is complete, participants will be provided with a dial-in number and conference code to access the call. A replay of the webcast will be available for a limited time following the event on the Investors and Media section of the Company’s website at View Source

On August 7, 2024 Revolution Medicines, Inc. (Nasdaq: RVMD), a clinical-stage oncology company developing targeted therapies for patients with RAS-addicted cancers, reported its financial results for the quarter ended June 30, 2024, and provided an update on corporate progress (Press release, Revolution Medicines, AUG 7, 2024, View Source [SID1234645502]).

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The company continues making progress on its 2024 development priorities:

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Advancing its RAS(ON) multi-selective inhibitor RMC-6236 into monotherapy pivotal trials.
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Pancreatic cancer: The company recently provided updated data on the clinical safety, tolerability and antitumor activity in patients with pancreatic ductal adenocarcinoma (PDAC) from its ongoing RMC-6236 monotherapy study. Strong preliminary progression-free survival (PFS) and overall survival (OS) PDAC data support the company’s plans to initiate a pivotal, randomized, controlled Phase 3 monotherapy study in the second-line (2L) treatment of patients with metastatic PDAC this year; work is underway toward this goal.
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Lung cancer: Data from the RMC-6236 monotherapy study in patients with non-small cell lung cancer (NSCLC) continue to mature. The company remains on track to initiate a pivotal study in previously-treated patients with RAS-mutated NSCLC this year.

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Expanding the reach of RMC-6236 monotherapy and/or combinations into earlier lines of therapy. Based on compelling preliminary monotherapy data in 2L PDAC, the company plans to evaluate RMC-6236 in earlier lines of treatment for pancreatic cancer including the first-line, locally advanced, and resectable settings. In addition to monotherapy, the company is currently evaluating RMC-6236 in combination with chemotherapy, which is the current standard of care for patients with PDAC.

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Qualifying its RAS(ON) mutant-selective inhibitors, RMC-6291 (G12C-selective inhibitor) and RMC-9805 (G12D-selective inhibitor), for late-stage development.
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With the goal of moving RMC-6291 into early lines of therapy in NSCLC, the company is currently evaluating the RAS(ON) inhibitor doublet of RMC-6291 with RMC-6236 as well as RMC-6291 with pembrolizumab.
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This doublet approach was recently highlighted in the Cancer Discovery publication that demonstrated robust antitumor activity by a RAS(ON) multi-selective inhibitor in combination with a RAS(ON) G12C-selective inhibitor in preclinical models of refractory KRAS G12X NSCLC.

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The company continues to enroll patients with solid tumors harboring KRAS G12D mutations in the RMC-9805 monotherapy study.

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In support of its continuing pipeline momentum and commercial ambitions, the company appointed Frank Clyburn to its board of directors; Mr. Clyburn is a distinguished executive who led Merck’s global Keytruda franchise from its inception and helped establish Merck as a global leader in oncology. The company also expanded its senior management group with key new hires in medical affairs, corporate affairs, drug safety and program leadership.

"Confidence in our RAS(ON) inhibitor platform and assets continues to grow and has been bolstered particularly by the strength of the interim safety, PFS and OS data shown in July for patients with pancreatic cancer in the RMC-6236 monotherapy study. Based on current benchmarks for first- and second-line treatment of metastatic PDAC, we believe RMC-6236 has the potential to become an important new therapeutic option to address large unmet medical needs for patients with this threatening disease," said Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. "The appointment of Frank Clyburn to our board of directors and several strategic additions to our executive team support our deep focus on enabling the next stage of growth and maturation for Revolution Medicines. We have made substantial progress in planning for the initiation of our first pivotal, Phase 3 study for RMC-6236 in pancreatic cancer, and are working actively to prepare to advance RMC-6236 into earlier lines of therapy."

Clinical Development Highlights

Plans to Advance RMC-6236 Monotherapy into Pivotal Trials

Pancreatic cancer: On July 15, 2024, the company reported updated data on the clinical safety, tolerability and antitumor activity from its ongoing monotherapy study evaluating RMC-6236 in patients with previously treated metastatic PDAC across dose cohorts ranging from 160 mg daily to 300 mg daily as of a May 11, 2024 data cutoff date. Key findings included:

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A total of 127 patients treated were evaluated for safety and tolerability.
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Approximately 22 percent of these patients experienced a Grade 3 or higher treatment-related adverse event (TRAE), and 96 percent of these patients experienced a TRAE of any grade.
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The most common TRAEs observed were rash and gastrointestinal-related toxicities. Reported TRAEs led to dose modifications (dose interruption and/or reduction) in 28 percent of these patients and there were no discontinuations due to TRAEs.
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The company also reported preliminary PFS and OS data in 2L treatment of patients with metastatic PDAC.
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The median PFS for patients with KRAS G12X mutations (n=42) was 8.1 months (95% confidence interval (CI); 5.9 months – not-estimable (NE)) and for patients with any RAS mutation (G12X, G13X and Q61X) (n=56) was 7.6 months (95% CI; 5.3 months – NE).
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For patients with KRAS G12X mutations and those with any RAS mutation, the observed OS was not estimable (95% CI for both groups; 8.5 months, NE).
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Based on initial feedback from the U.S. Food and Drug Administration, including supportive discussions on high-level trial design including a 300 mg daily dose, the company expects to initiate its Phase 3 registrational trial in the 2L treatment of patients with metastatic PDAC, called RASolute 302, this year.

Lung cancer: The company expects to share updated NSCLC data from its ongoing RMC-6236 monotherapy study in the fourth quarter of 2024 and to launch a registrational study to evaluate RMC-6236 in previously-treated patients with advanced NSCLC in the fourth quarter of 2024.

Evaluating RMC-6236 in Earlier Lines of Therapy

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PDAC. Evaluation is ongoing for RMC-6236 in combination with standard of care chemotherapy in first-line PDAC.

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NSCLC. Evaluation is ongoing for RMC-6236 in combination with pembrolizumab, with or without chemotherapy, in patients with advanced RAS-mutated NSCLC. The company expects to disclose initial clinical pharmacokinetic (PK), safety, tolerability and antitumor activity data for the combination of RMC-6236 with pembrolizumab in the fourth quarter of 2024.

Qualifying RMC-6291 for Late-Stage Development

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Combination Development. Evaluation of RMC-6291 with RMC-6236 and RMC-6291 with pembrolizumab, with or without chemotherapy, is ongoing. The company expects to disclose initial clinical PK, safety, tolerability and antitumor activity data for the combination of RMC-6291 with RMC-6236 in the fourth quarter of 2024 and for the combination RMC-6291 with pembrolizumab in the first half of 2025.

Qualifying RMC-9805 for Late-Stage Development

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Monotherapy Development. The company expects to disclose initial clinical PK, safety, tolerability and antitumor activity data for RMC-9805 in the fourth quarter of 2024.

RAS Innovation Engine

Beyond the first wave of clinical-stage RAS(ON) inhibitors, additional clinical development opportunities include the RAS(ON) mutant-selective inhibitors RMC-5127 (G12V), RMC-0708 (Q61H) and RMC-8839 (G13C) and the RAS companion inhibitors RMC-4630 (SHP2) and RMC-5552 (mTORC1/4EBP1).

On August 7, 2024 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported the following September 2024 investor events (Press release, Regeneron, AUG 7, 2024, View Source [SID1234645501]):

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Investor Conference Presentations

• Morgan Stanley 22nd Annual Global Healthcare Conference at 11:30 a.m. ET on
Wednesday, September 4, 2024

• 2024 Wells Fargo Healthcare Conference at 12:45 p.m. ET on Thursday,
September 5, 2024

The sessions may be accessed from the "Investors & Media" page of Regeneron’s website at View Source Replays and transcripts of the webcasts will be archived on the Company’s website for at least 30 days.

Oncology Webcast Information

• European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2024 conference call and webcast at 14:30 CEST/8:30 AM EDT on Monday, September 16, 2024

Regeneron will host a conference call and simultaneous webcast to share updates on the company’s oncology portfolio. A link to the webcast may be accessed from the ‘Investors and Media’ page of Regeneron’s website at View Source To participate via telephone, please register in advance at this link. Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number along with a unique passcode and registrant ID that can be used to access the call. A replay of the conference call and webcast will be archived on the company’s website for at least 30 days.

On August 7, 2024 Personalis, Inc. (Nasdaq: PSNL), a leader in advanced genomics for precision oncology, reported financial results for the second quarter ended June 30, 2024, and provided recent business accomplishments (Press release, Personalis, AUG 7, 2024, View Source [SID1234645500]).

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Recent Business Accomplishments

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Highlighted clinical performance of NeXT Personal at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) meeting in May
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Compelling breast cancer detection results were presented by Dr. Isaac Garcia-Murillas (Institute of Cancer Research, London) and Prof. Nicolas Turner (Royal Marsden NHS Foundation Trust UK). In this study, they found:
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NeXT Personal detected cancer recurrence approximately 15 months before imaging
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100% of patients that recurred were detected with NeXT Personal and 100% of patients that were ctDNA negative were cancer-free at follow up time points
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A presentation by Dr. Rodrigo Toledo of the Vall d’Hebron Institute of Oncology highlighted the importance of NeXT Personal’s use for immunotherapy monitoring. This data showed:
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Baseline levels of ctDNA and the changes detected by NeXT Personal predict therapy response and clinical outcomes for late-stage cancer patients receiving immunotherapy
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NeXT Personal detected cancer progression 81 days before imaging on average
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Delivered 561 total molecular tests in the second quarter of 2024, a 66% increase compared with the prior quarter, and commenced NeXT Personal Dx commercialization efforts with Tempus AI, Inc. (Tempus)
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Announced a cross-license agreement with Myriad Genetics, Inc. covering patent estates for tumor-informed approaches to detect minimal residual disease (MRD)
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Successfully settled the IP lawsuit with Foresight Diagnostics, Inc. (Foresight) with Foresight agreeing to license Personalis’ MRD patents

Second Quarter 2024 Results Compared to Second Quarter 2023

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Reported total company revenue of $22.6 million in the second quarter of 2024, an increase of 35% compared with $16.7 million
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Revenue from pharma testing and services of $13.2 million in the second quarter of 2024, an increase of 117% compared with $6.1 million

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Revenue from Enterprise customers of $8.0 million in the second quarter of 2024, an increase of 8% compared with $7.4 million
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Revenue from population sequencing for the U.S. Department of Veterans Affairs Million Veterans Program of $1.3 million in the second quarter of 2024, a decrease of 57% compared with $3.0 million
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Other Income of $3.0 million in the second quarter of 2024, which consists of a non-cash gain of $3.0 million related to fair-value accounting for the outstanding warrants issued to Tempus
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Net loss of $12.8 million in the second quarter of 2024, a decrease of 47% compared with $24.0 million
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Cash, cash equivalents, and short-term investments of $87.0 million as of June 30, 2024

"The revenue growth depicts growing customer confidence in both our technology and platform. Importantly, the growth in our clinical testing volume means that we can see the impact on patient lives. Now that our collaborators have presented compelling NeXT Personal clinical evidence, we expect to leverage that towards obtaining Medicare coverage and materially increasing the number of patients we can help," said Chris Hall, Chief Executive Officer. "As we continue to execute on our Win-in-MRD strategy, we are more confident than ever in our ability to drive broad adoption for patient testing."

Third Quarter and Revised Full Year 2024 Outlook

Personalis expects the following for the third quarter of 2024:

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Total company revenue in the range of $21.0 to $22.0 million
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Revenue from pharma tests, enterprise sales, and other customers in the range of $17.0 to $18.0 million
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Revenue from population sequencing of approximately $4.0 million

Personalis expects the following for the full year of 2024:

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Total company revenue in the range of $79.0 to $81.0 million, an increase from $76.0 to $78.0 million
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Revenue from pharma tests, enterprise sales, and all other customers in the range of $71.0 to $73.0 million, an increase from prior guidance of $68.0 to $70.0 million
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Revenue from population sequencing of approximately $8.0 million
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Non-GAAP net loss of approximately $75.0 million, a decrease from our prior guidance of $77.0 million and excludes any non-cash gain or loss from the outstanding warrants issued to Tempus
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Cash usage of approximately $60.0 million, a decrease from our prior guidance of $62.0 million

Webcast and Conference Call Information

Personalis will host a conference call to discuss the second quarter of 2024 financial results, as well as plans for 2024, after market close on Wednesday, August 7, 2024, at 2:00 p.m. Pacific Time / 5:00 p.m. Eastern Time. The conference call can be accessed live by dialing 800-717-1738 for domestic callers or 646-307-1865 for international callers. The live webinar can be accessed at View Source A replay of the webinar will be available shortly after the conclusion of the call and will be archived on the company’s website.

On August 7, 2024 Omeros Corporation (Nasdaq: OMER), a clinical-stage biopharmaceutical company committed to discovering, developing and commercializing small-molecule and protein therapeutics for large-market and orphan indications targeting immunologic disorders including complement-mediated diseases, as well as cancers and addictive and compulsive disorders, reported recent highlights and developments as well as financial results for the second quarter ended June 30, 2024, which include (Press release, Omeros, AUG 7, 2024, View Source [SID1234645499]):

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● Net loss for the second quarter of 2024 was $56.0 million, or $0.97 per share, compared to a net loss of $37.3 million, or $0.59 per share for the second quarter of 2023. For the six months ended June 30, 2024, our net loss was $93.2 million, or $1.60 per share, compared to a net loss of $71.0 million, or $1.13 per share in the prior year period. The second quarter of 2024 includes a $17.6 million charge for narsoplimab drug substance delivered during the quarter, the manufacturing of which commenced in October 2023, a $21.2 million payment for term loan-related debt repurchase, and $1.9 million of term loan-related transaction costs. These significant cash outlays, representing a total of $40.7 million dollars, are not expected to be repeated in the foreseeable future.

● On June 3, 2024, we entered into a Credit and Guaranty Agreement (the "Credit Agreement") with funds managed by Athyrium Capital Management (collectively, "Athyrium") and funds managed by Highbridge Capital Management (collectively, "Highbridge") as lenders (the "Lenders"). Under the Credit Agreement, we entered into an initial senior secured term loan of $67.1 million (the "Initial Term Loan") and paid $21.2 million to the Lenders in exchange for $118.1 million aggregate principal amount of Omeros’ existing 5.25 percent convertible senior notes due on February 15, 2026 (the "2026 Notes") held by the Lenders and representing 55 percent of our total 2026 Notes. The Credit Agreement also provides for a $25.0 million delayed draw term loan available to be drawn on request by Omeros on or prior to June 3, 2025 contingent on regulatory approval of narsoplimab in hematopoietic stem cell transplant-associated thrombotic microangiopathy ("TA-TMA"). All loans under the Credit Agreement have a stated maturity date of June 3, 2028.

ο The purchase price in the debt exchange and repurchase of our outstanding 2026 Notes represents a discount from notional value of approximately 25 percent.

ο Neither the Initial Term Loan nor the delayed draw term loan includes equity consideration for the Lenders, preventing any shareholder dilution as a consequence of these transactions.

ο After giving effect to the repurchase, we had approximately $98 million principal amount of our 2026 Notes outstanding.

● At June 30, 2024, we had $158.9 million of cash and short-term investments available for operations and debt servicing, a decrease of $12.9 million from December 31, 2023.

● As previously disclosed, we submitted an analysis plan to assess our existing clinical trial data along with other evidence proposed to be included in a resubmission of our biologics license application ("BLA") for narsoplimab in TA-TMA. We are engaged in ongoing discussions with the FDA regarding the analysis plan and the other evidence proposed to be included in the submission. An additional meeting with FDA has been scheduled and we expect to provide a further update on our plans for resubmission and anticipated timing when more definitive information becomes available.

● We continued advancing our lead MASP-3 inhibitor antibody zaltenibart (also known as OMS906) through a Phase 2 development program in paroxysmal nocturnal hemoglobinuria ("PNH") comprised of two fully enrolled clinical trials and a long-term extension study in which patients who have completed either of the first two studies are eligible to enroll. Patients continue to accrue to the extension study and we remain on track to initiate our Phase 3 program for zaltenibart in PNH later this year.

● Enrollment is ongoing in our Phase 2 clinical trial evaluating zaltenibart for the treatment of complement 3 glomerulopathy ("C3G"). A Phase 3 program in C3G is planned to begin in early 2025.

"Throughout the second quarter, we continued rapidly progressing our clinical programs while significantly strengthening our balance sheet," said Gregory A. Demopulos, M.D., Omeros’ chairman and chief executive officer. "Through the term loan and note repurchase transaction completed in June, we reduced by more than half the outstanding balance of our 2026 convertible notes at a substantial discount to par value without diluting shareholders. With the new secured term loan in place, a substantial portion of our outstanding debt is now maturing in 2028, the Company is well positioned to address the remaining balance of our 2026 convertible notes, and we have access to an additional term loan of up to $25 million to fund the commercial launch of narsoplimab in TA-TMA. Although the lengthy regulatory process is a continuing source of frustration for our team, our shareholders and, most especially, the TA-TMA patients in need of an effective treatment for this often-lethal condition, we believe that the evidence we have proposed to submit with our BLA is highly compelling and we remain dedicated to making narsoplimab the first approved product for the treatment of TA-TMA. We look forward to providing a further update on the outcome of our ongoing discussions with FDA. In parallel, our MASP-3 inhibitor zaltenibart continues to advance rapidly, generating consistently – and compared to other marketed and developing alternative pathway inhibitors – strong data, and it remains on track to initiate a Phase 3 program in PNH later this year and, in C3G, early in 2025."

Second Quarter and Recent Clinical Developments

● Recent developments regarding narsoplimab, our lead monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 ("MASP-2"), include the following:

o We previously submitted to FDA an analysis plan to assess already existing clinical trial data, existing data from an historical control population available from an external source, data from the narsoplimab expanded access (i.e., compassionate use) program, and data directed to the mechanism of action of narsoplimab. We are having ongoing discussions with the agency regarding the proposed analysis plan and FDA’s requirements for our resubmission of our BLA. An additional meeting with FDA has been scheduled and we expect to provide a further update on our plans for resubmission and the anticipated timing when more definitive information becomes available.

o FDA recently announced the establishment of the Rare Disease Innovation Hub, which will serve as a single point of connection and engagement within the FDA to support the development of treatments and products for rare diseases. The hub will have a particular focus on products intended for smaller populations or for diseases where the natural history is variable and not fully understood. FDA’s focus on these issues and their responsiveness to the rare disease community’s advocacy is encouraging, and we view the establishment of the hub as a tangible demonstration of FDA’s commitment to recognizing and addressing the unique challenges faced in developing therapies for these conditions.

ο In addition to previous publications on narsoplimab in TA-TMA, international transplant experts are preparing two manuscripts – one directed to the results of a survival comparison between our pivotal trial of narsoplimab in TA-TMA and an external control population of TA-TMA patients and the second detailing the survival data obtained from narsoplimab treatment of TA-TMA patients in our expanded access program. Physicians continue to request access to narsoplimab under this program for their patients with TA-TMA. Given that there is no approved treatment for this life-threatening condition, we continue to do what we can to help these patients.

● Recent developments regarding OMS1029, our long-acting, next-generation MASP-2 inhibitor, include:

o Both the single- and multiple-ascending-dose Phase 1 studies of OMS1029 have now been completed. The results support once-quarterly dosing, administered either subcutaneously or intravenously. Data from the multiple-ascending-dose study will be utilized to inform dose selection for continued clinical development. Consistent with the results of the single-ascending-dose Phase 1 clinical trial of OMS1029 completed in early 2023, OMS1029 was generally well tolerated at all doses evaluated in the multiple-ascending-dose study, with no significant safety concern identified to date.

o We continue to evaluate large market indications for Phase 2 clinical development of OMS1029. These include neovascular age-related macular degeneration, sometimes referred to as "wet AMD." MASP-2 inhibition previously showed efficacy in a pre-clinical murine model of wet AMD and we are currently engaged in a primate study comparing OMS1029 to Eylea (afibercept), a product currently approved to treat wet AMD. If shown to be effective, OMS1029 administered systemically (e.g., either intravenously or subcutaneously) could represent a significantly more attractive treatment experience compared to Eylea and other currently approved treatments for wet AMD, which require frequent injections directly into the posterior chamber of the eye.

● Recent developments regarding OMS906, our lead monoclonal antibody targeting mannan-binding lectin-associated serine protease-3 ("MASP-3"), the key activator of the alternative pathway, include:

o The United States Adopted Names Council ("USAN"), in consultation with the World Health Organization’s International Nonproprietary Names Expert Committee ("INN"), recently selected the nonproprietary name "zaltenibart" for OMS906. The USAN Council, by working closely with the INN Programme of the World Health Organization and various national nomenclature groups, aims for global standardization and unification of drug nomenclature to ensure that drug information is communicated accurately and unambiguously. Going forward, we will use the name zaltenibart to refer to our lead MASP-3 antibody in publications, at conferences and across other forums.

o Our Phase 2 trial evaluating two doses of zaltenibart in PNH patients who have had an unsatisfactory response to the C5 inhibitor ravulizumab has continued to produce encouraging data. The study utilizes a "switch-over" design, enrolling PNH patients who are receiving ravulizumab and adding zaltenibart to provide combination therapy with ravulizumab for 24 weeks. Those patients who demonstrate a hemoglobin response with the combination therapy are then switched to zaltenibart monotherapy. In June, at the annual congress of the European Hematology Association (EHA) (Free EHA Whitepaper), interim analysis results from the combination therapy portion of the trial were presented by Dr. Morag Griffin, an internationally recognized PNH expert from St. James University Hospital in England. During the adjunctive therapy period, the statistically significant mean hemoglobin improvement from baseline was 3.27 g/dL and 10 of 12 patients advanced to monotherapy. Absolute reticulocyte count also demonstrated statistically significant improvement. Zaltenibart was safe and well tolerated. An abstract providing results of the zaltenibart monotherapy stage has been submitted to the American Society of Hematology (ASH) (Free ASH Whitepaper) for presentation at their annual meeting in December. The efficacy and safety profiles of zaltenibart as monotherapy remain strong, including demonstration of sustained and clinically meaningful improvements in hemoglobin levels and absolute reticulocyte counts, as well as prevention of both extravascular and intravascular hemolysis.

o Our Phase 2 study of zaltenibart in PNH patients who have not previously received treatment with a complement inhibitor (i.e., naïve patients) is also ongoing and continues to progress well. Results from an interim analysis of subcutaneous zaltenibart treatment were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) meeting held in December 2023. Following that presentation, we amended the study protocol to identify the plasma concentrations and the level of MASP-3 inhibition required to inhibit breakthrough hemolysis. These data, in combination with data derived from our "switch-over" PNH study and from our Phase 1 studies in healthy subjects, are expected to provide all the data needed to finalize selection of the zaltenibart dose for our upcoming Phase 3 clinical trials.

o We plan to conduct two trials in our Phase 3 program for zaltenibart in PNH. Similar to our Phase 2 program, one will enroll complement inhibitor-naïve patients and the other will employ a "switch over" design. Through our recent advisory boards with experts in PNH and focus-group PNH patients, we have received valuable input to inform the design of our Phase 3 studies and our positioning of zaltenibart in the marketplace, if approved. The zaltenibart drug substance necessary to supply our Phase 3 clinical trials has been manufactured, upcoming pre-Phase 3 meetings with both European and U.S. regulators have been scheduled or requested, and the other activities required to initiate our Phase 3 program have also been completed or are progressing as planned. We remain on track to initiate the program later this year.

● Recent developments regarding OMS527, our phosphodiesterase 7 ("PDE7") inhibitor program focused on addictions and compulsive disorders as well as movement disorders, include:

o In April 2023 we were awarded a three-year, $6.69 million grant by the National Institute on Drug Abuse ("NIDA") to pursue development of our lead orally administered PDE7 inhibitor compound for the treatment of cocaine use disorder ("CUD"). We expect to complete by the end of this year a grant-funded preclinical cocaine interaction study, which is a safety prerequisite to initiation of the randomized, placebo-controlled, inpatient clinical study evaluating the safety and effectiveness of OMS527 in patients with CUD, which is also contemplated to be funded with proceeds of the NIDA award.