On August 8, 2024 Scholar Rock (NASDAQ: SRRK), a late-stage biopharmaceutical company focused on advancing innovative treatments for spinal muscular atrophy (SMA), cardiometabolic disorders, and other serious diseases where protein growth factors play a fundamental role, reported financial results and corporate updates for the second quarter ended June 30, 2024 (Press release, Scholar Rock, AUG 8, 2024, View Source [SID1234645625]).

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"Scholar Rock continues to execute across our portfolio of highly selective myostatin inhibition programs, further cementing our position as the global leader in harnessing the life-changing potential of TGF-beta superfamily biology," said Jay Backstrom, M.D., MPH, President & Chief Executive Officer of Scholar Rock. "With the only muscle-targeted program to demonstrate clinical proof-of-concept in SMA, our confidence in our lead program apitegromab continues to be supported by the clinical data generated over the past four years. At 48 months, over 90% of TOPAZ patients with nonambulatory SMA remained on apitegromab treatment on top of SMN therapy and we continued to observe sustained clinical benefit. We look forward to reporting topline data from the Phase 3 SAPPHIRE trial of apitegromab in SMA in the fourth quarter of this year."

Dr. Backstrom continued, "In addition, we are pleased with the progress of our cardiometabolic program. The enrollment of the Phase 2 proof-of-concept EMBRAZE study evaluating apitegromab in obesity has been advancing ahead of schedule and as a result, we are updating our guidance for topline data to the second quarter of 2025. We also presented new preclinical data supporting SRK-439’s potential to help patients retain lean muscle mass at our investor event in May and at the ADA 84th Scientific Sessions in June. The hallmark of our approach in designing both apitegromab and SRK-439 is the exquisite selectivity for pro- and latent forms of myostatin. Our data in SMA suggest that this selectivity matters for patients, and we are excited to show how SRK-439 can become an integral component of the treatment and management of obesity helping to preserve lean muscle mass for sustainable and healthy weight loss management."

Company Highlights and Upcoming Milestones

SMA Program

Apitegromab is an investigational, fully human monoclonal antibody that inhibits myostatin activation by selectively binding the pro- and latent forms of myostatin in skeletal muscle and is being developed as a potential first muscle-targeted therapy for the treatment of SMA. Apitegromab is the only muscle-targeted therapy to show clinical proof-of-concept in SMA.

● On track to report topline data from Phase 3 SAPPHIRE clinical trial in 4Q 2024. If the trial is successful and apitegromab is approved, the Company expects to initiate a commercial product launch in 2025.
● Reported that long-term apitegromab data continued to show substantial and sustained motor function improvements over 48 months1. The mean change in Hammersmith Functional Motor Scale (HFMSE) from baseline in nonambulatory patients (ages 2-21) on combination therapy (nusinersen and 20 mg/kg of apitegromab) was 5.3 points (95% CI: 1.5, 9.2; n=23), and for patients 2-12 was 6.4 points (95% CI: 1.8, 11.0, n=19). The mean change in RULM for the 2-21 age group was 3.6 points (95% CI: 2.0, 5.3; N=22) and for the 2-12 age group was 4.5 (95% CI: 2.7, 6.3; n=18). Of the 35 participants in the pooled nonambulatory population, 33 remained in the study over 4 years. The data analysis excluded the scores of 11 patients after undergoing scoliosis surgery, a known confounding factor for motor function assessment. Additional details will be discussed on the conference call this morning.

12-Month Data

24-Month Data

36-Month Data

48-Month Data

Age 2-21 Years Mean Change from Baseline in HFMSE (95% Confidence Interval)

3.6 points

(1.2, 6.0)

n=32

4.2 points

(1.9, 6.6)

n=29

4.0 points

(1.0, 6.9)

n=28

5.3 points

(1.5, 9.2)

n=23

Age 2-12 Years Mean Change from Baseline in HFMSE (95% Confidence Interval)

4.6 points

(1.8, 7.4)

n=26

5.2 points

(2.3, 8.0)

n=23

4.8 points

(1.3, 8.3)

n=23

6.4 points

(1.8, 11.0)

n=19

Age 2-21 Years Mean Change from Baseline in

RULM (95% Confidence Interval)

1.3 points

(0.2, 2.3)

n=31

2.3 points

(1.2, 3.3)

n=31

2.4 points

(1.1, 3.7)

n=27

3.6 points

(2.0, 5.3)

n=22

Age 2-12 Years Mean Change from Baseline in

RULM (95% Confidence Interval)

1.2 points

(0.1, 2.4)

n=25

2.2 points

(1.0, 3.5)

n=25

2.8 points

(1.4, 4.2)

n=22

4.5 points

(2.7, 6.3)

n=18

1. For the 48-month evaluation, an observed case analysis was conducted using available data by analysis timepoint, censoring any HFMSE and RULM assessments after the patient received scoliosis surgery. The analysis population pooled the nonambulatory patients (Cohorts 2 and 3) and included patients receiving either low dose (2 mg/kg) or high dose (20 mg/kg) apitegromab (inclusive of patients in Cohort 3 who switched from 2 mg/kg to 20 mg/kg in Year 2). A total of 11 patients in the population had scoliosis surgery during the study and their data was excluded from any HFMSE or RULM assessments at 48 months. Visit windows were applied to utilize data from unscheduled or early termination visits if the patient was missing the HFMSE or RULM total score at the scheduled visit.

● The ONYX open-label, multicenter extension study is ongoing. The extension study is evaluating the long-term safety and efficacy of apitegromab in patients with Type 2 and Type 3 SMA who completed the TOPAZ or SAPPHIRE trials. More than 90 percent of patients on combination therapy in the TOPAZ study have completed 4 years of apitegromab treatment and enrolled into ONYX.

Cardiometabolic Program

SRK-439 is a novel, preclinical, investigational myostatin inhibitor that has high in vitro affinity for pro- and latent myostatin and maintains myostatin specificity (i.e., no GDF11 or Activin A binding), and is initially being developed for the treatment of obesity.

● Presented preclinical data from the SRK-439 program. In May, the Company announced new preclinical data comparing SRK-439 and an anti-activin receptor II (anti-ActRII) antibody that supported SRK-439’s potential as best in class in preserving lean muscle mass in patients on GLP-1 receptor agonists (GLP-1 RAs). In June, the company presented new preclinical data at the American Diabetes Association 84th Scientific Sessions supporting the potential of SRK-439 to increase lean mass and contribute to a favorable body composition following withdrawal from GLP-1 RA treatment.
● Initiated Phase 2 EMBRAZE proof-of-concept trial with apitegromab in combination with a GLP-1 receptor agonist (GLP-1 RA) in obesity in May. The Phase 2 trial is a randomized, double-blind, placebo-controlled, multi-center study to evaluate the effect of apitegromab, a highly selective investigational myostatin inhibitor, to preserve muscle mass as an adjunctive therapy in overweight and obese adults who are taking a GLP-1 RA. Data are expected in the second quarter of 2025 and will be used to guide clinical development of SRK-439. The Company plans to file an IND for SRK-439 for the treatment of obesity in 2025.

Other Pipeline Updates

● New SRK-181 data from the Phase 1 DRAGON proof-of-concept trial presented at the ASCO (Free ASCO Whitepaper) Annual Meeting in June. SRK-181 is an investigational selective inhibitor of latent TGFβ-1 activation and developed with the aim of overcoming resistance to checkpoint therapy in patients with advanced cancer. Clinical data showed encouraging responses in heavily pretreated and anti-PD-(L)1 resistant patients across multiple tumor types. Enrollment of the DRAGON trial was completed in December 2023, and patients who remain on the study continue to be treated.
● Published data on SRK-373 was featured on the cover of Science Signaling in July. The article describes the selectivity of SRK-373 for LTBP-presented TGFβ-1, as well as efficacy data from two preclinical models that establish the feasibility of selectively targeting this particular form of TGFβ-1 for the treatment of fibrosis. SRK-373 is an investigational selective inhibitor of matrix associated TGFβ-1 in development for the treatment of fibrosis.

Second Quarter 2024 Financial Results

For the quarter ended June 30, 2024, net loss was $58.5 million or $0.60 per share compared to a net loss of $37.9 million or $0.47 per share for the quarter ended June 30, 2023.

● The Company did not record any revenue for the quarter ended June 30, 2024 or for the quarter ended June 30, 2023.
● Research and development expense was $42.4 million for the quarter ended June 30, 2024, compared to $26.9 million for the quarter ended June 30, 2023. The increase was primarily attributable to clinical trial and employee compensation costs.
● General and administrative expense was $17.1 million for the quarter ended June 30, 2024, compared to $12.2 million for the quarter ended June 30, 2023. The increase was due to employee-related costs.
● As of June 30, 2024, Scholar Rock had cash, cash equivalents, and marketable securities of approximately $190.5 million, which is expected to fund the Company’s anticipated operating and capital expenditure requirements into the second half of 2025.

"Our year-to-date progress across our pipeline of industry-leading myostatin inhibition programs, combined with our highly experienced and disciplined team, provides us with a robust foundation for growth as we advance towards multiple milestones and our potential evolution into a commercial-stage company," said Ted Myles, Chief Operating Officer and Chief Financial Officer of Scholar Rock.

Conference Call Information
Management will provide an update on the Company and discuss second quarter 2024 results via conference call on Thursday, August 8 at 8:15 am ET. To access the live conference call, participants may register here. The live audio webcast of the call will be available under "Events and Presentations" in the Investor Relations section of the Scholar Rock website at View Source To participate via telephone, please register in advance here. 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. An archived replay of the webcast will be available on the Company’s website for approximately 90 days.

About Apitegromab

Apitegromab is an investigational fully human monoclonal antibody inhibiting myostatin activation by selectively binding the pro- and latent forms of myostatin in the skeletal muscle. It is the first muscle-targeted treatment candidate to demonstrate clinical proof-of-concept in spinal muscular atrophy (SMA). Myostatin, a member of the TGFβ superfamily of growth factors, is expressed primarily by skeletal muscle cells, and the absence of its gene is associated with an increase in muscle mass and strength in multiple animal species, including humans. Scholar Rock believes that its highly selective targeting of pro- and latent forms of myostatin with apitegromab may lead to a clinically meaningful improvement in motor function in patients with SMA. The U.S. Food and Drug Administration (FDA) has granted Fast Track, Orphan Drug and Rare Pediatric Disease designations, and the European Medicines Agency (EMA) has granted Priority Medicines (PRIME) and Orphan Medicinal Product designations, to apitegromab for the treatment of SMA. The efficacy and safety of apitegromab have not been established and apitegromab has not been approved for any use by the FDA or any other regulatory agency.

About the Phase 3 SAPPHIRE Trial

SAPPHIRE is an ongoing randomized, double-blind, placebo-controlled, Phase 3 clinical trial evaluating the safety and efficacy of apitegromab in nonambulatory patients with Types 2 and 3 SMA who are receiving SMN-targeted therapy (either nusinersen or risdiplam). SAPPHIRE targeted enrolling approximately 156 patients aged 2-12 years old in the main efficacy population. These patients were randomized 1:1:1 to receive for 12 months either apitegromab 10 mg/kg, apitegromab 20 mg/kg, or placebo by intravenous (IV) infusion every 4 weeks. An exploratory population that targeted enrolling up to 48 patients aged 13-21 years old will also separately be evaluated. These patients were randomized 2:1 to receive either apitegromab 20 mg/kg or placebo. For more information about SAPPHIRE, visit www.clinicaltrials.gov. Apitegromab has not been approved for any use by the US FDA or any other health authority, and its safety and efficacy have not been established.

About EMBRAZE

EMBRAZE is a randomized, double-blind, placebo-controlled, Phase 2 proof-of-concept trial evaluating the efficacy, safety and pharmacokinetics of apitegromab in adults with a body mass index (BMI) of >27 (overweight) or a BMI of >30 (obese) and taking a GLP-1 RA (tirzepatide or semaglutide). The target enrollment of EMBRAZE is 100 subjects aged 18-65 who are overweight or obese without diabetes. As part of the study design, the treatment period is 24 weeks, and all subjects will receive a GLP-1 RA. In addition, all subjects will be randomized 1:1 to receive either apitegromab or placebo by intravenous (IV) infusion every four weeks during the 24-week treatment period. The primary endpoint is change from baseline at Week 24 in lean mass assessed by dual-energy X-ray absorptiometry. Secondary endpoints include additional weight loss measures, safety and tolerability, and pharmacokinetic outcomes. Exploratory endpoints at Weeks 24 and 32 include cardiometabolic parameters (e.g. HbA1c), body composition, and physical function.

About SRK-439

SRK-439 is a novel, preclinical, investigational myostatin inhibitor that has high in vitro affinity for pro- and latent myostatin and maintains myostatin specificity (i.e., no GDF11 or Activin-A binding), and is initially being developed for the treatment of cardiometabolic disorders, including obesity. Based on preclinical data, SRK-439 has the potential to support healthier weight management by preserving lean mass during weight loss. The efficacy and safety of SRK-439 have not been established and SRK-439 has not been approved for any use by the FDA or any other regulatory agency.

On August 7, 2024 Aclaris Therapeutics, Inc. (NASDAQ: ACRS), a clinical-stage biopharmaceutical company focused on developing novel drug candidates for immuno-inflammatory diseases, reported its financial results for the second quarter of 2024 and provided a corporate update (Press release, Aclaris Therapeutics, AUG 7, 2024, View Source [SID1234645482]).

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"With study activities underway for our ATI-2138 Phase 2a trial in moderate to severe atopic dermatitis and the strengthening of our balance sheet through the completion of our royalty purchase agreement with OMERS, we’re well-positioned to drive our strategic initiatives forward," said Dr. Neal Walker, Interim President & CEO and Chair of the Board of Directors of Aclaris. "Our focus remains on leveraging our resources to maximize the potential of our innovative drug candidates, pursue available opportunities, and create long-term value for patients and shareholders alike."

Research and Development Highlights:

ITK Inhibitor Programs
ATI-2138, an investigational oral covalent ITK/JAK3 inhibitor
ATI-2138-AD-201: Aclaris is activating clinical sites and expects to enroll patients in the coming weeks in this Phase 2a open-label trial to investigate the safety, tolerability, pharmacokinetics, efficacy, and pharmacodynamics of ATI-2138 in subjects with moderate to severe atopic dermatitis (AD).
ITK Selective Compound
Aclaris is progressing to development candidate selection a second generation ITK selective inhibitor for autoimmune indications.
Lepzacitinib (ATI-1777), an investigational topical "soft" JAK 1/3 inhibitor
In January 2024, Aclaris reported positive top-line results from its Phase 2b trial of lepzacitinib in atopic dermatitis (AD).
Aclaris is currently seeking a global development and commercialization partner for this program (excluding Greater China). As previously announced, in 2022 Aclaris granted Pediatrix Therapeutics exclusive rights to develop and commercialize lepzacitinib in Greater China.
Zunsemetinib (ATI-450), an investigational oral small molecule MK2 inhibitor
Aclaris plans to support Washington University in St. Louis in its investigator-initiated Phase 1b/2 trials of zunsemetinib as a potential treatment for pancreatic cancer and metastatic breast cancer. Aclaris expects these trials to be primarily funded by grants awarded to Washington University.
Financial Highlights:

Liquidity and Capital Resources

As of June 30, 2024, Aclaris had aggregate cash, cash equivalents and marketable securities of $149.9 million compared to $181.9 million as of December 31, 2023. In July 2024, Aclaris received an upfront payment of $26.5 million and is eligible to receive up to an additional $5.0 million upon the achievement of certain sales milestones in connection with the sale of OLUMIANT royalties and milestones to OMERS Life Sciences.

Aclaris anticipates that its cash, cash equivalents and marketable securities as of June 30, 2024 in combination with the $26.5 million from the sale of OLUMIANT royalties and milestones will be sufficient to fund its operations into 2028, without giving effect to any potential new business development transactions, additional financing activities or the outcome of its strategic review.

Financial Results

Second Quarter 2024

Net loss was $11.0 million for the second quarter of 2024 compared to $29.6 million for the second quarter of 2023.
Total revenue was $2.8 million for the second quarter of 2024 compared to $1.9 million for the second quarter of 2023. The increase was primarily driven by an increase in royalties under the Lilly license agreement during the three months ended June 30, 2024.
Research and development (R&D) expenses were $8.8 million for the quarter ended June 30, 2024 compared to $25.3 million for the prior year period.
The $16.5 million decrease was primarily the result of lower:
Zunsemetinib development expenses associated with clinical activities for a Phase 2a trial for hidradenitis suppurativa which was completed in March 2023, a Phase 2b trial for rheumatoid arthritis which was completed in November 2023, a Phase 2b trial for psoriatic arthritis which was discontinued in December 2023, and drug candidate manufacturing costs;
Costs associated with lepzacitinib preclinical development activities and a Phase 2b clinical trial for AD which was completed in January 2024;
ATI-2138 development expenses, including costs associated with a Phase 1 MAD trial which was completed in September 2023 and other preclinical activities; and
Compensation-related expenses due to a decrease in headcount and higher forfeiture credits.
General and administrative (G&A) expenses were $4.8 million for the quarter ended June 30, 2024 compared to $8.3 million for the prior year period. The decrease was primarily due to a reduction in compensation-related expenses due to lower headcount and higher forfeiture credits, along with the recognition of bad debt expense recorded in the prior year period from Aclaris’ determination that collection of amounts due from EPI Health are uncertain as a result of their filing for Chapter 11 bankruptcy protection.
Licensing expenses were $1.3 million for the quarter ended June 30, 2024 compared to $0.6 million for the prior year period. The increase was due to an increase in royalties earned under the Lilly license agreement.
Revaluation of contingent consideration resulted in a $0.2 million loss for the quarter ended June 30, 2024 compared to a gain of $1.5 million for the prior year period.
Year-to-date 2024

Net loss was $27.9 million for the six months ended June 30, 2024 compared to $57.7 million for the six months ended June 30, 2023.
Total revenue was $5.2 million for the six months ended June 30, 2024 compared to $4.4 million for the six months ended June 30, 2023. The increase was primarily driven by an increase in royalties under the Lilly license agreement during the six months ended June 30, 2024.
R&D expenses were $18.6 million for the six months ended June 30, 2024 compared to $47.9 million for the prior year period.
The $29.3 million decrease was primarily the result of lower:
Zunsemetinib development expenses associated with clinical activities for a Phase 2a trial for hidradenitis suppurativa which was completed in March 2023, a Phase 2b trial for rheumatoid arthritis which was completed in November 2023, a Phase 2b trial for psoriatic arthritis which was discontinued in December 2023, and drug candidate manufacturing costs;
Costs associated with lepzacitinib preclinical development activities and a Phase 2b clinical trial for AD which was completed in January 2024;
ATI-2138 development expenses, including costs associated with a Phase 1 MAD trial which was completed in September 2023 and other preclinical activities; and
Compensation-related expenses due to a decrease in headcount and higher forfeiture credits.
G&A expenses were $11.6 million for the six months ended June 30, 2024 compared to $17.1 million for the prior year period. The decrease was primarily due to a reduction in compensation-related expenses due to lower headcount and higher forfeiture credits, a decrease in patent, legal and accounting related expenses, and the recognition of bad debt expense recorded in the prior year period from Aclaris’ determination that collection of amounts due from EPI Health are uncertain as a result of their filing for Chapter 11 bankruptcy protection.
Licensing expenses were $2.3 million for the six months ended June 30, 2024 compared to $1.6 million for the prior year period. The increase was due to an increase in royalties earned under the Lilly license agreement.
Revaluation of contingent consideration resulted in a $3.0 million loss for the six months ended June 30, 2024 compared to a gain of $2.3 million for the prior year period.
OLUMIANT is a registered trademark of Eli Lilly and Company.

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.

On August 7, 2024 Agenus Inc. (NASDAQ: AGEN), a leader in developing novel immunological agents to treat various cancers, reported the publication of a seminal study in the prestigious Cancer Discovery, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), detailing the novel mechanism of action and effectiveness of botensilimab, an investigational, novel multifunctional anti-CTLA-4 antibody, in various treatment-resistant cancers (Press release, Agenus, AUG 7, 2024, View Source [SID1234645521]).

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The paper, entitled "Botensilimab, an Fc-Enhanced Anti-CTLA-4 Antibody, Is Effective Against Tumors Poorly Responsive to Conventional Immunotherapy," highlights several key findings:

Demonstrated Activity Across Multiple Cancers: Botensilimab has shown increased activity in multiple treatment-resistant cancers, including those that have progressed on prior checkpoint inhibitors.
Fc-Enhanced Design for Multifunctional Immune Activation: Unlike traditional anti-CTLA-4 antibodies, botensilimab’s Fc-enhanced design allows it to leverage multiple immune-activating mechanisms simultaneously. This includes enhanced T cell priming, reduction of intratumoral regulatory T cells, and activation of antigen-presenting cells, leading to a robust anti-tumor response.
Activity Independent of Conventional Limitations: Botensilimab shows clinical activity regardless of factors that typically limit conventional immunotherapy efficacy, such as tumor neoantigen burden and FcγRIIIA genotype. This broadens its potential applicability across diverse patient populations.
Remodeling the Tumor Microenvironment: The antibody uniquely remodels the tumor microenvironment, transforming "cold" tumors that are currently unresponsive to immune therapies into "hot" immunologically active tumors. This is achieved by reducing regulatory T cells and increasing T cell inflammation gene signatures within the tumor microenvironment.
Promise in Difficult-to-Treat Cancers: Botensilimab demonstrates significant promise in treating over nine difficult-to-treat cancers, including microsatellite stable colorectal cancer and may extend clinical benefits to patient populations historically unresponsive to conventional immune checkpoint inhibitors.
"We are thrilled to share these groundbreaking findings with the scientific community," said Dhan Chand, PhD, lead author and Vice President of Research at Agenus. "The compelling preclinical and clinical evidence generated with botensilimab reveal an actionable pathway to improve treatment outcomes and extend survival to patient populations historically unresponsive to conventional immune checkpoint inhibitors."

This paper underscores the potential of botensilimab to overcome some of the most challenging hurdles in cancer treatment, offering new hope to patients with limited options. Agenus is committed to advancing this promising therapy through further clinical development and regulatory pathways to ensure rapid and broad patient access.

About Cancer Discovery

Cancer Discovery publishes high-impact, peer-reviewed articles describing major advances in research and clinical trials. As the premier cancer information resource, the Journal also presents Review Articles, Perspectives and Commentaries, News stories, and Research Watch summaries of important journal articles to its readers to keep them informed about the latest findings in the field. Topics span the spectrum of cancer research and medicine from the laboratory to the clinic and epidemiologic studies.

About Botensilimab

Botensilimab is an investigational human Fc-enhanced CTLA-4 blocking antibody designed to boost both innate and adaptive anti-tumor immune responses. Its novel design leverages mechanisms of action to extend immunotherapy benefits to "cold" tumors which generally respond poorly to standard of care or are refractory to conventional PD-1/CTLA-4 therapies and investigational therapies. Botensilimab augments immune responses across a wide range of tumor types by priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells and inducing long-term memory responses.

Approximately 1,100 patients have been treated with botensilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with Agenus’ investigational PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers. For more information about botensilimab trials, visit www.clinicaltrials.gov with the identifiers NCT03860272, NCT05608044, NCT05630183, and NCT05529316.

On August 7, 2024 Assertio Holdings, Inc. ("Assertio" or the "Company") (Nasdaq: ASRT), a pharmaceutical company with comprehensive commercial capabilities oering dierentiated products to patients, today reported nancial results for the second quarter ended June 30, 2024 (Press release, Assertio Holdings, AUG 7, 2024, View Source [SID1234647065]).

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"In my rst two months at Assertio, I have been excited to work closely with the team, meet our growing list of oncology clinic customers and focus on how best to maximize our results going forward. The second quarter’s performance illustrates how we continue to diligently execute the three pillars of Assertio’s business plan: driving the nancial performance of Assertio’s key assets, including our lead asset Rolvedon, generating cash ow and identifying new assets to create further value for our stockholders," said Brendan O’Grady, who was appointed Chief Executive Ocer on May 29, 2024.

"Rolvedon has been well received by physicians and continues to increase its share of the oncology G-CSF market,
generating its sixth consecutive quarter of demand growth since launch. As a potential opportunity for further
dierentiation, we have also completed enrollment of Rolvedon’s same-day dosing trial and expect to present the
initial data at a medical conference later this year. Combined with the rest of our platform and pipeline of
prospective business development opportunities, I am excited about the potential for Assertio."