On August 8, 2024 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage biotechnology company developing first-in-classi targeted and immune-mediated therapeutics to fight cancer, reported financial results for the quarter ended June 30, 2024, and provided a corporate update (Press release, Tempest Therapeutics, AUG 8, 2024, View Source [SID1234645626]).

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"During the second quarter, amezalpat demonstrated positive survival benefit as a potential treatment for first-line liver cancer patients," said Stephen Brady, president and chief executive officer of Tempest. "Improving survival for these patients with the right safety profile is our goal and is also the primary global regulatory endpoint for this indication. This remarkable six-month improvement in survival compared to the standard of care, and maintenance of a strong hazard ratio, gives us confidence in the potential success of the program. These data point to the potential of amezalpat to help HCC patients in a meaningful way, and we’re excited to be moving the program towards a pivotal study."

Recent Highlights

Amezalpat (TPST-1120) (clinical PPARα antagonist):
Reported new positive survival data from the ongoing global randomized Phase 1b/2 clinical study demonstrating amezalpat (TPST-1120) delivered a six-month improvement in median overall survival ("OS") when combined with atezolizumab and bevacizumab in comparison to atezolizumab and bevacizumab alone in the first-line treatment of patients with unresectable or metastatic HCC. At the cutoff date of February 14, 2024, the new data from 40 patients randomized to the amezalpat arm and 30 patients randomized to the control arm showed:
21-month median OS for the amezalpat arm versus 15 month for the control arm, a six-month survival advantage
20/40 patients remain in survival follow up in the amezalpat arm, compared to 9/30 patients in the control arm
The survival benefit was maintained across key subpopulations
0.65 hazard ratio ("HR") for OS, revealing a stable HR since the top-line analysis 10 months earlier when the HR was 0.59
Manageable safety profile consistent with Phase 1 data
Reported new preclinical data at the 2024 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting demonstrating that amezalpat reduces kidney cancer growth as a monotherapy, while also showing increased inhibition when combined with frontline chemotherapy and immunotherapy. These data further support the clinical benefit observed in the TPST-1120 Phase 1 data presented in an oral presentation at ASCO (Free ASCO Whitepaper) 2022.
Published positive data from Phase 1 Trial of amezalpat in patients with advanced solid tumors in the Journal of Cancer Research Communications. Data showed that amezalpat demonstrated clinical activity, including tumor shrinkage, even in PD-1 inhibitor-refractory and immune-compromised cancers, and was well tolerated both as monotherapy and in combination with nivolumab. These data complement the positive Phase 1b/2 data reported in October 2023 from a global randomized study of amezalpat in combination with atezolizumab and bevacizumab in first-line patients with advanced HCC.
Potential Future Milestones

Amezalpat (TPST-1120) (clinical PPARα antagonist)
Plan to advance amezalpat into a registrational Phase 3 study in first-line HCC patients, subject to obtaining feedback from the FDA.
TPST-1495 (clinical dual EP2/4 prostaglandin receptor antagonist)
Plan to advance TPST-1495 into a Phase 2 study in patients with Familial Adenomatous Polyposis ("FAP") in 2024 under the auspices of the Cancer Prevention Clinical Trials Network and funded by the National Cancer Institute ("NCI") Division of Cancer Prevention, subject to final approval of NCI.
Expect to report data from the combination arm at the two highest TPST-1495 doses in patients with advanced endometrial cancer, where prostaglandin signaling is implicated, in 2024.
Financial Results

Second Quarter 2024

Tempest ended the quarter with $31.1 million in cash and cash equivalents, compared to $39.2 million on December 31, 2023.
Net loss and net loss per share for the quarter ended June 30, 2024, were $9.6 million and $0.42, respectively, compared to $7.6 million and $0.54, respectively, for the same period in 2023.
Research and development expenses for the quarter were $5.8 million compared to $4.4 million for the same period in 2023. The $1.4 million increase was primarily due to an increase in costs incurred from contract research and manufacturing organizations, as well as stock-based compensation.
General and administrative expenses for the quarter were $3.7 million compared to $3.1 million for the same period in 2023. The $0.6 million increase was primarily due to an increase in stock-based compensation expense as well as legal and consulting services.
Year-to-Date

Cash used in operating activities for the six months ended June 30, 2024 was $12.7 million.
Net loss and net loss per share for the six months ended June 30, 2024 were $17.5 million and $0.78, respectively, compared to $15.2 million and $1.09, respectively, for the same period in 2023.
Research and development expenses for the six months ended June 30, 2024 were $10.2 million compared to $9.1 million for the same period in 2023. The $1.1 million increase was primarily due to an increase in costs incurred from contract research and manufacturing organizations, as well as stock-based compensation.
General and administrative expenses for the six months ended June 30, 2024 were $7.4 million compared to $6.0 million for the same period in 2023. The $1.4 million increase was primarily due to an increase in stock-based compensation expense as well as legal and consulting services.

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 8, 2024 Sanofi reported new results from the two-part, double-randomized, German-speaking Myeloma Multicenter Group (GMMG)-HD7 phase 3 study show that Sarclisa (isatuximab) in combination with lenalidomide, bortezomib, and dexamethasone (RVd) during induction therapy in transplant-eligible, newly diagnosed multiple myeloma (NDMM) significantly prolonged progression-free survival (PFS) from first randomization, resulting in a statistically significant and clinically meaningful reduction in disease progression or death, compared to RVd induction regardless of the maintenance regimen (Press release, Sanofi, AUG 8, 2024, View Source [SID1234645624]). Full results will be submitted for presentation at a forthcoming medical meeting.

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Hartmut Goldschmidt, MD
President of GMMG, Professor of Medicine at the Heidelberg University Hospital (UKHD), Germany and principal investigator of the study
"Successful induction therapy is one of the most critical components to reduce the relapse or recurrence risk in patients with newly diagnosed multiple myeloma. While we observed this investigational combination showed improved minimal residual disease negativity rates in the bone marrow, indicating potentially deeper responses after induction, further follow-up was needed to better understand how this translated to long-term outcomes. These data provide evidence that the Isa-RVd regimen potentially improves progression-free survival in the frontline, transplant-eligible population and supports the potential of this quadruplet to become a new standard-of-care induction regimen in this treatment setting."

GMMG-HD7 is one of six phase 3 studies to report positive results for Sarclisa in patients with multiple myeloma, which includes four positive readouts of a Sarclisa-based quadruplet in the frontline setting. The most recent included results from the IMROZ phase 3 study evaluating the investigational use of Sarclisa with VRd versus VRd for patients with transplant-ineligible NDMM, demonstrating a statistically significant and clinically meaningful improvement in PFS and a higher proportion of patients with minimal residual disease (MRD) negativity.

Dietmar Berger, MD, PhD
Chief Medical Officer and Global Head of Development at Sanofi
"The GMMG-HD7 study was designed to better understand the distinct effect of targeting CD38 with Sarclisa in induction versus maintenance treatment of transplant-eligible patients. These data build upon our belief that Sarclisa has the potential to be a best-in-class CD38 therapy that could improve long-term outcomes versus the standard-of-care for certain patients. We look forward to the full data presentation and continuing our mission of helping make a meaningful difference for people living with multiple myeloma."

In December 2021, Sanofi and GMMG shared the results from part one, which met the primary endpoint of MRD negativity after induction therapy and before transplant in NDMM patients. The GMMG-initiated study is being conducted in close collaboration with Sanofi based on jointly defined research. Sanofi provided financial support to GMMG for this study. The use of Sarclisa in combination with RVd is investigational and has not been evaluated by any regulatory authority.

While considered a rare disease, MM is the second most common hematologic malignancy,1 with more than 180,000 new diagnoses of MM worldwide yearly.2 Despite available treatments, MM remains an incurable malignancy in most patients with an estimated 61% five-year survival rate for newly diagnosed patients.3 Since MM does not have a cure, most patients will relapse. Relapsed MM is the term for when the cancer returns after treatment or a period of remission. Refractory MM refers to when the cancer does not respond or no longer responds to therapy.

About the GMMG-HD7 study
GMMG-HD7 is a pivotal randomized, open-label, multicenter, 2-part phase 3 study evaluating Sarclisa in combination with RVd versus RVd induction followed by post-transplant re-randomization to Sarclisa plus lenalidomide versus lenalidomide maintenance in transplant-eligible NDMM patients. The study enrolled 662 patients with transplant-eligible NDMM across 67 sites in Germany. In the first part of the study, all participants were equally randomized to receive three 42-day cycles of RVd in both arms of the study, while Sarclisa was added to only one study arm. In the second part of the study, patients were re-randomized post-transplant to receive Sarclisa plus lenalidomide or lenalidomide alone as maintenance therapy. During the study, Sarclisa was administered through an intravenous infusion at a dose of 10 mg/kg once weekly for the first four weeks of cycle one, then every other week for the rest of the induction period.

MRD negativity was assessed by next-generation flow cytometry (sensitivity of 1×10-5) after induction. In the latest readout of the study, PFS for both Sarclisa plus RVd as an induction therapy, regardless of maintenance treatment, and Sarclisa plus lenalidomide as a maintenance regimen were measured from first randomization.

GMMG-HD7 protocol defined the primary endpoints of MRD negativity after induction treatment for the first part of the study, and PFS following the second randomization after transplant for part two of the study, in which Sarclisa was added to lenalidomide maintenance, with the latter primary endpoint anticipated to be available at a later date. The key secondary endpoint for the first part of the study was PFS from first randomization. Additional secondary endpoints included rates of complete response after induction, and intensification, overall survival, and safety.

About Sarclisa
Sarclisa (isatuximab) is a monoclonal antibody that binds to a specific epitope on the CD38 receptor on MM cells, inducing distinct antitumor activity. It is designed to work through multiple mechanisms of action including programmed tumor cell death (apoptosis) and immunomodulatory activity. CD38 is highly and uniformly expressed on the surface of MM cells, making it a target for antibody-based therapeutics such as Sarclisa.

Based on the ICARIA-MM phase 3 study, Sarclisa is approved in more than 50 countries, including the US and the EU, in combination with pomalidomide and dexamethasone for the treatment of patients with relapsed refractory MM (RRMM) who have received ≥2 prior therapies, including lenalidomide and a proteasome inhibitor and who progressed on last therapy. Based on the IKEMA phase 3 study, Sarclisa is also approved in 50 countries in combination with carfilzomib and dexamethasone, including in the US for the treatment of patients with RRMM who have received 1–3 prior lines of therapy and in the EU for patients with MM who have received at least one prior therapy. In the US, the non-proprietary name for Sarclisa is isatuximab-irfc, with irfc as the suffix designated in accordance with nonproprietary naming of biological products guidance for industry issued by the US Food and Drug Administration.

Sarclisa continues to be evaluated in multiple ongoing phase 3 clinical studies in combination with current standard treatments across the MM treatment continuum. It is also under investigation for the treatment of other hematologic malignancies, and its safety and efficacy have not been evaluated by any regulatory authority outside of its approved indication.

Sanofi is committed to pursuing the advancement of Sarclisa through several investigational studies across the MM treatment continuum. Various patient-centric clinical development programs aim to bring Sarclisa to more patients, intercept the disease earlier in the treatment journey, and explore potential new combinations including assessing subcutaneous administration via a proprietary on body device system. The safety and efficacy of Sarclisa has not been evaluated by any regulatory authority outside of its approved indications and methods of delivery.

In striving to become the number one immunoscience company globally, there is a commitment to advancing oncology innovation. The pipeline is being reshaped and prioritized, leveraging expertise in immunoscience to drive progress. Efforts are centered on select hematologic malignancies and solid tumors with critical unmet needs, including multiple myeloma, acute myeloid leukemia, certain types of lymphomas, as well as gastrointestinal and lung cancers.

For more information on Sarclisa clinical studies, please visit www.clinicaltrials.gov.

About the German-speaking Myeloma Multicenter Group (GMMG)
GMMG is the largest study group focusing on MM in Germany, with headquarters based in Heidelberg. Within the last 20+ years, the GMMG study group has performed numerous studies including five randomized, multicenter phase 3 studies with 4,000 patients enrolled from about 90 participating and co-treating centers throughout Germany. The overall goal of GMMG is to generate improved therapies for myeloma patients through the development and testing of novel and personalized, genome- and signaling-driven treatment strategies. The GMMG has set itself the goal of achieving further approvals for effective antibody-based drug combinations for the first-line treatment of myeloma patients, in which antibody-based treatment regimens have been integrated into seven GMMG study concepts (CONCEPT, DANTE, DADA, HD6, HD7, HD8, HD9 and HD10).

On August 8, 2024 Sana Biotechnology, Inc. (NASDAQ: SANA), a company focused on creating and delivering engineered cells as medicines, reported financial results and business highlights for the second quarter 2024 (Press release, Sana Biotechnology, AUG 8, 2024, View Source [SID1234645623]).

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"The hypoimmune platform addresses one of the fundamental challenges with allogeneic cell transplantation and has the opportunity to impact a broad range of diseases," said Steve Harr, Sana’s President and Chief Executive Officer. "We have four ongoing trials and are pleased with the progress and encouraged by our learnings in the clinic to-date. We are accelerating investments to build our pivotal-ready supply chain, decrease our reliance on external manufacturing given ongoing geopolitical uncertainty, and increase our clinical trial site footprint globally. We continue the dose escalation phases of our studies, which makes predicting the numbers of patients and release date for data an inexact science, but we look forward to reporting clinical data in each therapeutic area later this year with the goal of an initial understanding of the safety and efficacy profiles."

Recent Corporate Highlights

Advancing four clinical programs across seven indications, including an allogeneic CAR T program targeting CD19+ cancers, an allogeneic CAR T program for B-cell mediated autoimmune diseases, an allogeneic CAR T program for cancer patients that have failed a CD19-targeted therapy, and a gene-modified primary islet cell therapy in type 1 diabetes:

Oncology – The ARDENT trial evaluates SC291, a hypoimmune (HIP)-modified CD19-directed allogeneic CAR T therapy, in patients with B-cell malignancies. Early SC291 data from the ongoing ARDENT trial suggest the ability to dose safely, the desired immune evasion profile, and early clinical efficacy. The VIVID trial evaluates SC262, a HIP-modified CD22-directed allogeneic CAR T therapy, in patients with relapsed or refractory B-cell malignancies who have received prior CD19-directed CAR T therapy. Sana is enrolling patients in both studies and expects to share data in 2024.

B-cell Mediated Autoimmune Diseases – The GLEAM trial evaluates SC291 in patients with B-cell mediated autoimmune diseases including lupus nephritis, extrarenal lupus, and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Sana is enrolling patients in this study and expects to share initial data in 2024.

Type 1 Diabetes – UP421 is a primary human HIP-modified pancreatic islet cell therapy for patients with type 1 diabetes. The goal of this investigator-sponsored trial (IST) is to understand immune evasion, islet cell survival, and beta cell function, as measured by C-peptide production, of HIP-modified pancreatic islet cells in type 1 diabetics without any immunosuppression. Initial screening took longer than anticipated, and after a protocol amendment to expand the eligible patient pool, multiple patients are now enrolled and awaiting donor availability. Sana awaits initial patient dosing at Uppsala University Hospital and expects to share initial data in 2024.
Published preclinical data in Nature Biotechnology showing that healthy transplanted human glial progenitor cells replaced diseased glial cell population in a preclinical model:

In the study, human glial chimeric mice were used to model the impact of competition between healthy and diseased human glia in vivo. When wild-type (WT) healthy human glial progenitor cells (hGPCs) were transplanted into adult mice that had been neonatally chimerized with mutant Huntingtin (mHTT)-expressing hGPCs, the healthy cells outcompeted and ultimately eliminated diseased glia, repopulating the brain with the healthy cells.
These data establish additional proof-of-concept for the development of SC379, Sana’s pluripotent stem cell (PSC)-derived glial progenitor cell (GPC) product candidate, as a potential therapy to deliver healthy allogeneic GPCs to patients with certain central nervous system disorders.
Second Quarter 2024 Financial Results

GAAP Results

Cash Position: Cash, cash equivalents, and marketable securities as of June 30, 2024 were $251.6 million compared to $205.2 million as of December 31, 2023. The increase of $46.4 million was primarily driven by net proceeds from equity financings of $181.0 million, proceeds from stock option exercises and the employee stock purchase plan of $8.4 million, and proceeds of $7.6 million from a loan to fund tenant improvements for our manufacturing facility in Bothell, Washington during the six months ended June 30, 2024, partially offset by cash used in operations of $124.2 million and cash used for the purchase of property and equipment of $28.9 million.

Research and Development Expenses: For the three and six months ended June 30, 2024, research and development expenses, inclusive of non-cash expenses, were $60.9 million and $117.3 million, respectively, compared to $73.0 million and $140.2 million for the same periods in 2023. The decreases of $12.1 million and $22.9 million for the three and six months ended June 30, 2024, respectively, compared to the same periods in 2023 were primarily due to lower personnel-related and laboratory costs due to a decrease in headcount and decreased research costs related to the strategic repositioning in the fourth quarter of 2023, lower costs for third-party manufacturing at contract development and manufacturing organizations, and a decline in facility and other allocated costs. These decreases were partially offset by increased clinical development costs and an increase in costs for the acceleration of internal manufacturing capabilities, further de-risking of the supply chain. Research and development expenses include non-cash stock-based compensation of $7.1 million and $13.0 million, respectively, for the three and six months ended June 30, 2024 and $6.7 million and $12.7 million, for the same periods in 2023.
Research and Development Related Success Payments and Contingent Consideration: For the three and six months ended June 30, 2024, Sana recognized a non-cash gain of $27.9 million and a non-cash expense of $10.1 million, respectively, in connection with the change in the estimated fair value of the success payment liabilities and contingent consideration in aggregate, compared to non-cash expenses of $26.7 million and $26.8 million for the same periods in 2023. The value of these potential liabilities fluctuate significantly with changes in Sana’s market capitalization and stock price.

General and Administrative Expenses: General and administrative expenses for the three and six months ended June 30, 2024, inclusive of non-cash expenses, were $16.4 million and $32.7 million, respectively, compared to $16.6 million and $33.3 million for the same periods in 2023. The decrease of $0.2 million for the three months ended June 30, 2024 compared to the same period in 2023 was primarily due to a decrease in costs related to Sana’s previously planned manufacturing facility in Fremont, California, lower personnel-related costs due to a decrease in headcount related to the strategic repositioning in the fourth quarter of 2023, and a decrease in legal fees. These decreases were partially offset by an increase in non-cash stock-based compensation and consulting fees. The decrease of $0.6 million for the six months ended June 30, 2024 compared to the same period in 2023 was primarily due to a decrease in costs related to Sana’s previously planned manufacturing facility in Fremont, California and lower personnel-related costs due to a decrease in headcount related to the strategic repositioning in the fourth quarter of 2023. These decreases were partially offset by an increase in non-cash stock-based compensation, legal fees, and consulting costs.

Net Loss: Net loss for the three and six months ended June 30, 2024 was $50.3 million, or $0.21 per share, and $157.8 million, or $0.70 per share, respectively, compared to $114.0 million, or $0.59 per share, and $196.1 million, or $1.02 per share for the same periods in 2023.

On August 8, 2024 Replimune Group, Inc. (Nasdaq: REPL), a clinical stage biotechnology company pioneering the development of a novel class of oncolytic immunotherapies, reported financial results for the fiscal first quarter ended June 30, 2024 and provided a business update (Press release, Replimune, AUG 8, 2024, View Source [SID1234645622]).

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"We have had a highly productive quarter as we gear up for the upcoming pre-BLA meeting with the FDA and prepare to enroll the first patient in our confirmatory trial of RP1 in anti-PD1 failed melanoma," said Sushil Patel, Ph.D., CEO of Replimune. "Our confidence in the RP1 program is reinforced by the IGNYTE primary analysis data that we presented in June, which demonstrates the potential of RP1 to address unmet needs in anti-PD1 failed melanoma patients who have not responded to prior existing therapies. We remain committed to advancing the clinical programs in our pipeline, including RP2, where we are preparing to enroll patients in a registration-directed study in uveal melanoma."

Program Highlights & Milestones

RP1

RP1 combined with Opdivo (nivolumab) in anti-PD1 failed melanoma
In June, the Company announced positive topline primary analysis data by independent central review from the IGNYTE clinical trial of RP1 plus nivolumab in anti-PD1 failed melanoma. Topline results showed the 12-month overall response rate was 33.6% by modified RECIST 1.1 criteria, the primary endpoint as defined in the protocol, and 32.9% by RECIST 1.1 criteria, an additional analysis requested by the FDA. Responses from baseline were highly durable, with all responses lasting more than 6 months and median duration of response exceeding 35 months.
The Company plans to present the full primary analysis data from the anti-PD1 failed melanoma cohort including key secondary endpoint data and subgroups for presentation at an upcoming medical congress.
The Company expects to enroll its first patient in the Phase 3 confirmatory IGNYTE-3 trial in Q3 2024, prior to submitting the RP1 BLA expected in 2H 2024. The Phase 3 trial design has been agreed to with the FDA and will be a 2-arm randomized trial with a defined list of physician’s choice treatment options as the comparator arm in advanced melanoma patients who progressed on anti-PD1 and anti-CTLA-4 therapy or are ineligible for anti-CTLA-4 treatment.
A pre-BLA meeting with the FDA is scheduled for September and a BLA submission is planned for 2H 2024.
RP2

RP2 in Uveal Melanoma
In June during ASCO (Free ASCO Whitepaper) 2024, the Company presented safety, efficacy, and biomarker results from an open-label, multicenter, Phase 1 study of RP2 alone or combined with nivolumab in a cohort of patients with uveal melanoma. RP2 administered as monotherapy or in combination with nivolumab demonstrated an ORR of 29.4%, with a disease control rate (DCR) of 58.8%.
Replimune has finalized the protocol based on FDA input and begun trial initiation activities for a registration-directed study of RP2 in metastatic uveal melanoma in patients who are immune checkpoints inhibitor-naïve. The study is a randomized trial of RP2 in combination with nivolumab vs. ipilimumab and nivolumab, or nivolumab for those ineligible for ipilimumab.

RP2 in Hepatocellular Carcinoma (HCC)
A Phase 2 clinical trial with RP2 combined with atezolizumab and bevacizumab in anti-PD1/PD-L1 progressed HCC is expected to dose its first patient in 2H 2024.
Financial Highlights

Financing: Completed a securities purchase agreement for a private investment in public equity ("PIPE") raising $96.7 million net of issuance costs. Proceeds from the financing will be used to scale up for the commercialization of RP1 and for working capital and general corporate purposes.

Cash Position: As of June 30, 2024, cash, cash equivalents and short-term investments were $469.1 million, as compared to $420.7 million as of fiscal year ended March 31, 2024. The increase in cash balance was directly related to the PIPE financing, offset by cash utilized in operating activities in advancing the Company’s clinical development plans.

Based on the current operating plan, the Company believes that existing cash, cash equivalents and short-term investments, as of June 30, 2024 will enable the Company to fund operations into the second half of 2026 which includes scale up for the commercialization of RP1 in skin cancers and for working capital and general corporate purposes.
R&D Expenses: Research and development expenses were $43.0 million for the fiscal first quarter ended June 30, 2024, as compared to $40.4 million for the fiscal first quarter ended June 30, 2023. This increase was primarily due to increased personnel expenses, including a $2.8 million increase in payroll and fringe benefits, and a stock-based compensation increase of $0.9 million. Research and development expenses included $4.2 million in stock-based compensation expenses for the fiscal first quarter ended June 30, 2024.

S,G&A Expenses: Selling, general and administrative expenses were $14.4 million for the fiscal first quarter ended June 30, 2024, as compared to $15.2 million for the fiscal first quarter ended June 30, 2023. Selling, general and administrative expenses included $5.2 million in stock-based compensation expenses for the fiscal first quarter ended June 30, 2024.

Net Loss: Net loss was $53.8 million for the fiscal first quarter ended June 30, 2024, as compared to a net loss of $49.6 million for the fiscal first quarter ended June 30, 2023.
About RP1
RP1 (vusolimogene oderparepvec) is Replimune’s lead product candidate and is based on a proprietary strain of herpes simplex virus engineered and genetically armed with a fusogenic protein (GALV-GP R-) and GM-CSF intended to maximize tumor killing potency, the immunogenicity of tumor cell death, and the activation of a systemic anti-tumor immune response.

About RP2
RP2 is based on a proprietary strain of herpes simplex virus engineered and genetically armed with a fusogenic protein (GALV-GP R-) and GM-CSF intended to maximize tumor killing potency, the immunogenicity of tumor cell death and the activation of a systemic anti-tumor immune response. RP2 additionally expresses an anti-CTLA-4 antibody-like molecule, as well as GALV-GP R- and GM-CSF. RP2 is intended to provide targeted and potent delivery of these proteins to the sites of immune response initiation in the tumor and draining lymph nodes, with the goal of focusing systemic-immune-based efficacy on tumors and limiting off-target toxicity.