On November 14, 2022 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, reported that highlights results from a retrospective multi-center study of 32 patients evaluating the safety of antegrade administration of JELMYTO (mitomycin) for pyelocalyceal solution via percutaneous nephrostomy tube for the treatment of patients with upper tract urothelial carcinoma (UTUC) (Press release, UroGen Pharma, NOV 14, 2022, View Source [SID1234624028]). The study titled, "Antegrade Administration of Mitomycin Gel for UTUC via Percutaneous Nephrostomy Tube: A Multi-Institutional Retrospective Cohort Study," provides additional real-world evidence of a favorable safety and tolerability profile for JELMYTO when administered via percutaneous nephrostomy tube and is published in The British Journal of Urology International, November Issue.

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This retrospective study assessed the safety and feasibility of antegrade administration of JELMYTO via a percutaneous nephrostomy tube (PCNT) in 32 patients from four institutions. Each patient received at least one dose of JELMYTO via PCNT for UTUC, 29 of whom completed induction (at least 5 of 6 doses) and underwent primary disease evaluation (PDE) at a median 17 weeks after the last dose of therapy. At a median follow-up of 15 months following initiation of induction therapy, ureteral stenosis (defined as a discrete narrowing of the ureter on direct visual ureteroscopy, or a constriction identified on retrograde pyelogram at the time of ureteroscopy that required dilation or stenting to pass a ureteroscope for upstream visualization) occurred in three (9%) of patients. None of these patients had recurrent stenosis at a median 16 months follow- up. Other adverse events included fatigue (27%), flank pain (19%), urinary tract infection (12%), sepsis (8%), and hematuria (8%). No patient had impaired renal function during follow-up and there were no treatment-related deaths. Seventeen patients (59%) had no evidence of disease at PDE and had not recurred at a median follow-up of 13 months post induction.

"We found that antegrade administration of JELMYTO via a nephrostomy tube offered a low rate of ureteral stenosis and a favorable safety and tolerability profile overall," said Kyle Rose, M.D., Urologic Oncology Fellow at Moffitt Cancer Center in Tampa, Fla., and study investigator. "This study adds to the evidence that this form of administration is beneficial in many ways, including the ability to treat the elderly without the use of anesthesia, which can have negative cumulative effects when used repetitively."

In both retrograde and antegrade approaches, JELMYTO can be administered as an outpatient procedure in the clinic. Retrograde administration requires administration by a physician via a ureteral catheter which requires fluoroscopic guidance. Antegrade administration may be performed by trained nursing professionals under clean rather than sterile conditions and does not require fluoroscopy once tube placement is confirmed via nephrostogram at the first instillation.

"JELMYTO is approved for antegrade and retrograde administration in patients with LG-UTUC, which gives physicians the added convenience of choosing a method that works best for them and their patients," said Mark Schoenberg, Chief Medical Officer, UroGen. "Retrograde administration was the only method used in the pivotal OLYMPUS trial. Therefore, UroGen is pleased that this study adds to the growing body of real-world evidence demonstrating that antegrade administration of JELMYTO is a feasible alternative for patients with LG-UTUC."

About the Retrospective Study

In this multi-center study, patients undergoing antegrade administration of JELMYTO via PCNT were retrospectively included for analysis from four tertiary referral centers between 2020 and 2022. The primary outcome was safety profile graded by Common Terminology Criteria for Adverse Events (v5.0). Post-therapy disease burden was assessed by primary disease evaluation (PDE) via ureteroscopy. Thirty-two patients received at least one dose of JELMYTO via PCNT for UTUC, 29 of whom completed induction and underwent PDE. Thirteen (41%) patients had residual tumor present prior to induction therapy. At a median follow up of 15 months following first dose of induction therapy, ureteral stenosis occurred in 3 (9%) patients, all of which were treated without later recurrence or chronic stenosis. Other adverse events included fatigue (27%), flank pain (19%), UTI (12%), sepsis (8%), and hematuria (8%). No patients had impaired renal function during follow up and there were no treatment related deaths. Seventeen patients (59%) had no evidence of disease at PDE and had not recurred at a median follow up of 13 months post induction.

Limitations of this study include the retrospective nature and sample size. Some complications and side effects of the antegrade approach were contingent on patient reporting, and thus may be under-reported. Ureteral stenoses were noted incidentally at the time of PDE, and no patients presented with obstructive symptoms. There is a need for larger studies with longer follow-up to study more conclusively any potential advantages of antegrade JELMYTO administration when compared to retrograde instillation.

About the Pivotal OLYMPUS Study

OLYMPUS (Optimized DeLiverY of Mitomycin for Primary UTUC Study) was an open-label, single-arm Phase 3 clinical study of UGN-101 JELMYTO (mitomycin) for pyelocalyceal solution, to evaluate the safety, tolerability and tumor ablative effect of JELMYTO in patients with low-grade Upper Tract Urothelial Cancer UTUC (LG UTUC). Seventy-one patients were treated at clinical sites across the United States and Israel. Study participants were treated with six weekly instillations of JELMYTO administered via a standard catheter. Four to six weeks following the last instillation, patients underwent a Primary Disease Evaluation (PDE) to determine Complete Response (CR), the primary endpoint of the study. PDE involved a ureteroscopy and wash cytology, a standard microscopic test of cells obtained from the urine to detect cancer and for cause biopsy. Patients who achieved a CR at the PDE timepoint were eligible for the maintenance phase of the trial, during which they could receive monthly maintenance instillations for up to 12 months and were assessed to determine the durability of response with JELMYTO.

In the OLYMPUS study, data was generated for the retrograde administration of JELMYTO. In that study, population ureteric obstruction was reported in 58% (n=41) of patients receiving JELMYTO, including 17% (n=12) of patients who experienced Grade 3 obstruction.

About LG UTUC

LG UTUC is a rare disease managed by endoscopic methods and radical nephroureterectomy. Endoscopic resection and laser ablation attempt to preserve the kidney, though there is a high risk of recurrence that may eventually necessitate removal of the kidney. Although kidney removal is the gold standard for treatment of high-grade UTUC, it may be over-treatment in LG UTUC, as kidney removal offers similar five-year survival as kidney-sparing procedures but is associated with significant morbidity. JELMYTO is efficacious as a primary chemoablative therapy in patients with LG UTUC.

About JELMYTO

JELMYTO (mitomycin) for pyelocalyceal solution is a mitomycin-containing reverse thermal gel containing 4 mg mitomycin per mL gel indicated for primary chemoablative treatment of LG UTUC in adults. It is recommended for primary treatment of biopsy-proven LG UTUC in patients deemed appropriate candidates for renal-sparing therapy. JELMYTO is a viscous liquid when cooled and becomes a semi-solid gel at body temperature. The drug slowly dissolves over four to six hours after instillation and is removed from the urinary tract by normal urine flow and voiding. It is approved for administration in a retrograde manner via ureteral catheter or antegrade through nephrostomy tube. The delivery system allows the initial liquid to coat and conform to the upper urinary tract anatomy. The eventual semisolid gel allows for chemoablative therapy to remain in the collecting system for four to six hours without immediately being diluted or washed away by urine flow.

APPROVED USE FOR JELMYTO

JELMYTO is a prescription medicine used to treat adults with a type of cancer of the lining of the upper urinary tract including the kidney called low-grade Upper Tract Urothelial Cancer (LG-UTUC).

IMPORTANT SAFETY INFORMATION

You should not receive JELMYTO if you have a hole or tear (perforation) of your bladder or upper urinary tract.

Before receiving JELMYTO, tell your healthcare provider about all your medical conditions, including if you:

are pregnant or plan to become pregnant. JELMYTO can harm your unborn baby. You should not become pregnant during treatment with JELMYTO. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with JELMYTO.
Females who are able to become pregnant: You should use effective birth control (contraception) during treatment with JELMYTO and for 6 months after the last dose.

Males being treated with JELMYTO: If you have a female partner who is able to become pregnant, you should use effective birth control (contraception) during treatment with JELMYTO and for 3 months after the last dose.

are breastfeeding or plan to breastfeed. It is not known if JELMYTO passes into your breast milk. Do not breastfeed during treatment with JELMYTO and for 1 week after the last dose.
Tell your healthcare provider if you take water pills (diuretic).
How will I receive JELMYTO?

Your healthcare provider will tell you to take a medicine called sodium bicarbonate before each JELMYTO treatment.
You will receive your JELMYTO dose from your healthcare provider 1 time a week for 6 weeks. It is important that you receive all 6 doses of JELMYTO according to your healthcare provider’s instructions. If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment. Your healthcare provider may recommend up to an additional 11 monthly doses.
JELMYTO is given to your kidney through a tube called a catheter.
During treatment with JELMYTO, your healthcare provider may tell you to take additional medicines or change how you take your current medicines.
After receiving JELMYTO:

JELMYTO may cause your urine color to change to a violet to blue color. Avoid contact between your skin and urine for at least 6 hours.
To urinate, males and females should sit on a toilet and flush the toilet several times after you use it. After going to the bathroom, wash your hands, your inner thighs, and genital area well with soap and water.
Clothing that comes in contact with urine should be washed right away and washed separately from other clothing.
JELMYTO may cause serious side effects, including:

Swelling and narrowing of the tube that carries urine from the kidney to the bladder (ureteric obstruction). If you develop swelling and narrowing, and to protect your kidney from damage, your healthcare provider may recommend the placement of a small plastic tube (stent) in the ureter to help the kidney drain. Tell your healthcare provider right away if you develop side pain or fever during treatment with JELMYTO.
Bone marrow problems. JELMYTO can affect your bone marrow and can cause a decrease in your white blood cell, red blood cell, and platelet counts. Your healthcare provider will do blood tests prior to each treatment to check your blood cell counts during treatment with JELMYTO. Your healthcare provider may need to temporarily or permanently stop JELMYTO if you develop bone marrow problems during treatment with JELMYTO.
The most common side effects of JELMYTO include: urinary tract infection, blood in your urine, side pain, nausea, trouble with urination, kidney problems, vomiting, tiredness, stomach (abdomen) pain.

You are encouraged to report negative side effects of prescription drugs to the U.S. Food and Drug Administration. Visit www.fda.gov/medwatch or call 1‑800‑FDA‑1088. You may also report side effects to UroGen Pharma at 1-855-987-6436.

On November 14, 2022 TransCode Therapeutics, Inc. (NASDAQ: RNAZ), the RNA oncology company committed to more effectively treating cancer using RNA therapeutics, reported financial results for the third quarter ended September 30, 2022, and recent business progress (Press release, TransCode Therapeutics, NOV 14, 2022, View Source [SID1234624027]).

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"We continued to advance our therapeutic programs during the third quarter," said Michael Dudley, co-founder, president and CEO of TransCode. "We remain on track to achieve our planned milestones for 2H of 2022 which include submission of an exploratory Investigational New Drug Application (eIND) this year for our planned Phase 0 clinical trial in up to 12 cancer patients with advanced solid tumors. We continue to make strides in development of our therapeutic candidates in our pipeline, all of which utilize our proprietary TTX delivery platform. These include our immuno-oncology candidates, TTX-siPDL1 and TTX-RIGA, as well as TTX-mRNA, each of which has the potential to treat multiple solid tumor indications."

"In addition to the progress towards filing our eIND for our First-in-Human (FIH) clinical study, we were granted orphan drug designation by the US Food and Drug Administration (FDA) for TTX-siPDL1 for pancreatic cancer, and we continued preclinical studies with other therapeutic candidates in a variety of tumor indications," added Dudley.

TransCode co-founder and Chief Technology Officer, Dr. Zdravka Medarova, commented, "We have made substantial progress towards further advancement of our therapeutic candidates, TTX-MC138 and TTX-siPDL1, for the treatment of cancer, including pancreatic adenocarcinoma, which has a dismal prognosis and for which there are few therapeutic options. This focus on cancers associated with a poor prognosis and modestly successful conventional treatment options is driven by the broad applicability of our therapeutic candidates to multiple indications and reflects our philosophy that targeted RNA-based treatments could deliver much needed success where traditional cytotoxic approaches have failed. In addition to our progress on the research front, we have completed eIND-enabling studies to support our upcoming First-in-Human trial with our lead therapeutic candidate, TTX-MC138."

Commenting on the current environment for biotech company stocks, Dudley noted, "The biotech sector has lost tremendous value starting in the second half of 2021 and continuing in 2022. Many public companies in the sector are trading at or below enterprise value. We firmly believe that our current stock price does not in any way reflect the value we have created since we completed our IPO in July 2021. We continue our R&D efforts to de-risk our therapeutic candidates with the goal of bringing to market cancer therapeutics that we believe could offer longer term survival benefits over current cancer therapeutics, and to build long term value for our shareholders.

Recent Business Highlights

·In July 2022, TransCode announced expansion of its intellectual property portfolio through the filing of a provisional patent application (US 63/356,449) entitled RADIOLABELED NANOPARTICLES AND TEMPLATE DIRECTED IMMUNOMODULATION FOR CANCER THERAPY (the ‘449 application). TransCode expects to convert the ‘449 application into an international application in approximately one year.

·In August 2022, TransCode and The University of Texas MD Anderson Cancer Center (MD Anderson) announced a strategic alliance to advance TransCode’s pipeline of RNA-targeted oncology therapeutic and diagnostic candidates. Through the alliance, TransCode and MD Anderson scientists plan to collaborate on preclinical studies to further validate TransCode’s therapeutic and diagnostic candidates and to expand the reach of TransCode’s discovery engine. The results of these studies will inform future clinical trials with these agents, including trials to be led at MD Anderson.
·In September 2022, TransCode announced the appointment of Frank J. Slack, PhD, to its advisory board. Dr. Slack is the Shields Warren Mallinckrodt Professor, Department of Pathology, and Director of the Harvard Medical School Initiative for RNA Medicine (HIRM), Beth Israel Deaconess Medical Center. Directed by Dr. Slack, the HIRM Initiative seeks to harness the potential of RNA to revolutionize the way cancer and other diseases are treated and diagnosed. Having pioneered pivotal studies proving that microRNAs drive oncogenesis and represent critical targets for the treatment of cancer, his guidance is expected to prove highly valuable as TransCode enters the clinical phase of development.

Subsequent to the end of the third quarter, TransCode reported positive preclinical results with its immunotherapy candidate, TTX-siPDL1, in pancreatic adenocarcinoma. After two weekly treatments of study animals with TTX-siPDL1 combined with the standard-of-care chemotherapeutic, gemcitabine, tumor volumes were 25% of those in untreated animals. By the fifth week of treatment, 75% of animals treated with TTX-siPDL1 plus gemcitabine were still alive versus 25% of those treated with gemcitabine alone. Additionally, immune cell profiling of tumors from the treated animals indicated successful PD-L1 inhibition and immune cell activation, consistent with the known mechanism-of-action (MOA) of checkpoint inhibitors. Because TTX-siPDL1 incorporates a silencing RNA (siRNA) against PD-L1 as its functional component, it has the potential to trigger the degradation and/or translational repression of the PD-L1 messenger RNA (mRNA), preventing the tumor cell from expressing the PD-L1 antigen altogether.

TransCode also recently reported positive preclinical results with its lead candidate, TTX-MC138, in a murine model of pancreatic adenocarcinoma. The drug demonstrated a pharmacodynamic response by successfully inhibiting its target, microRNA-10b (miR-10b), as measured by qRT-PCR, a commonly used assay for measuring gene expression. Serum miR-10b, a possible surrogate biomarker of therapeutic efficacy, was down-regulated by TTX-MC138 in this study. Forty percent (40%) of animals treated with TTX-MC138 had complete regression of disease and long-term survival without recurrence. TransCode believes that, combined, this study and the study with TTX-siPDL1 described above in pancreatic cancer models further demonstrate successful delivery of therapeutic candidates to genetic targets inside tumor cells with our proprietary TTX delivery system.

Planned Milestones

TransCode’s goals to continue to advance its portfolio include:

·TTX-MC138
oSubmission to FDA of an eIND application for its First-in-Human Phase 0 clinical trial.
oCompletion of the FIH clinical trial intended to demonstrate quantifiable evidence of delivery of radiolabeled TTX-MC138 to metastatic lesions in advanced solid tumors; measure pharmacokinetics and biodistribution in vital organs and other tissues; potentially inform therapeutic dose levels for future trials based on microdose results; and validate delivery for the TTX pipeline more broadly, potentially opening-up additional relevant RNA targets that have been previously undruggable due to challenges with RNA delivery.

oCompletion of IND-enabling studies to support filing an IND application for a Phase I clinical trial of TTX-MC138.

·Completion of preclinical in vivo studies supporting the lead therapeutic candidate, TTX-MC138, in pancreatic cancer and glioblastoma multiforme, among others.
·Completion of preclinical in vivo studies supporting therapeutic candidates, TTX-siPDL1, TTX-RIGA, and TTX-siLIN28B.
·Continuation of discussions regarding potential partnerships.
·Filing for orphan drug designation for TTX-MC138 in additional tumor indications including pancreatic cancer.

Third Quarter 2022 Financial Highlights

·Cash was $8.8 million at September 30, 2022, compared to $20.8 million at December 31, 2021, which does not include up to approximately $1.8 million expected from the Small Business Innovation Research (SBIR) grant we were awarded in 2021 comprising approximately $928 thousand available for year two of the award, the current year, and up to $870 thousand related to year three of the award.
·Research and development expenses were $3.0 million in the third quarter of 2022, compared to $993 thousand in the third quarter of 2021.
·General and administrative expenses were $1.9 million in the third quarter of 2022, compared to $1.4 million in the third quarter of 2021.
·Operating loss for the three months ended September 30, 2022, was $4.95 million, compared to an operating loss of $2.36 million in the prior year period.

Financial Guidance

TransCode expects that its cash of $8.8 million at September 30, 2022, along with approximately $928 thousand of additional year-two funding from our SBIR grant award, is sufficient to fund planned operations through the first quarter 2023 but not for a full 12 months from the date of its financial statements.

On November 14, 2022 TRACON Pharmaceuticals, Inc. (Nasdaq: TCON), a clinical stage biopharmaceutical company utilizing a cost-efficient, CRO-independent product development platform to advance its pipeline of novel targeted cancer therapeutics and to partner with other life science companies, reported financial results for the third quarter ended September 30, 2022 (Press release, Tracon Pharmaceuticals, NOV 14, 2022, View Source [SID1234624026]). The Company will host a conference call and webcast today at 4:30 PM Eastern Time / 1:30 PM Pacific Time.

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"Enrollment in the ENVASARC Phase 2 pivotal trial continues to be ahead of schedule and we look forward to reporting the interim efficacy analysis on the initial 36 patients in the fourth quarter, after each patient has had two on-study scans," said Charles Theuer, M.D., Ph.D., President and CEO of TRACON. "Additionally, we have been notified by the ICC Tribunal that it is far along in its deliberations but invited additional information on two discrete issues and requested arbitration costs prior to determining the final award of the binding arbitration with I-Mab. We now expect to receive the decision in the first quarter of 2023."

Recent Corporate Highlights

In August, we announced that the U.S. Food and Drug Administration (FDA) approved our Investigational New Drug (IND) application for the initiation of a Phase 1/2 clinical trial of our CTLA-4 antibody YH001 in combination with envafolimab and doxorubicin for the treatment of sarcoma patients, including patients who have not received prior therapy.

In September, we announced entry into a $35 million non-dilutive long-term debt facility with Runway Growth Finance Corp., with $10 million funded at closing which extended the Company’s runway to mid-2023.

In September, we announced that we received fast track designation from the FDA for the development of envafolimab for patients with locally advanced, unresectable or metastatic undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS) who have progressed on one or two prior lines of chemotherapy.

In October, the Independent Data Monitoring Committee (IDMC) recommended the ENVASARC Phase 2 pivotal trial proceed as planned following the review of more than 12 weeks of safety data from more than 20 patients who received the 600 mg dose of envafolimab as a single agent or in combination with Yervoy (ipilimumab).
Expected Upcoming Milestones

Report the interim efficacy analysis by the IDMC following the review of more than 12 weeks of efficacy data from 36 patients who received the 600 mg dose of envafolimab as a single agent or in combination with Yervoy.

Initiate dosing in the Phase 1/2 clinical trial of envafolimab with our potential best in class CTLA-4 antibody YH001, as well as with doxorubicin chemotherapy.

Report the binding decision of the International Chamber of Commerce (ICC) Arbitration Panel on the ongoing arbitration involving the TJ4309 and bispecific antibody agreements with I-Mab Biopharma where we are seeking to recover over $200 million in damages, which we expect in the first quarter of 2023.
Third Quarter 2022 Financial Results

Cash and cash equivalents were $17.0 million at September 30, 2022, compared to $24.1 million at December 31, 2021, and is expected to fund the company into mid-2023.

Research and development expenses for the third quarter of 2022 were $4.1 million, compared to $2.7 million for the third quarter of 2021.

General and administrative expenses for the third quarter of 2022 were $2.3 million, compared to $4.2 million for the third quarter of 2021. The decrease was primarily attributable to legal expenses incurred in the third quarter of 2021 due to the arbitration with I-Mab.

Net loss for the third quarter of 2022 was $6.4 million, compared to $7.0 million for the third quarter of 2021.
Conference Call Details

To access the call by phone, please register using this link and you will be provided with dial-in details.

A live webcast of the conference call will be available online from the Investor/Events and Presentation page of the Company’s website at www.traconpharma.com.

After the live webcast, a replay will remain available on TRACON’s website for 60 days.

About Envafolimab

Envafolimab (KN035), a single-domain antibody against PD-L1 invented by Alphamab Oncology, is the first approved subcutaneously injected PD-(L)1 inhibitor. Envafolimab was approved by the Chinese NMPA in November 2021 in adult patients with MSI-H/dMMR advanced solid tumors who failed systemic treatment and have no satisfactory alternative treatment options. In December 2019, Alphamab Oncology, 3D Medicines and TRACON entered into a collaboration whereby TRACON has the right to develop and commercialize envafolimab in soft tissue sarcoma in North America. Envafolimab is currently being studied in the pivotal ENVASARC Phase 2 trial in the United States sponsored by TRACON and a Phase 3 pivotal trial in combination with gemcitabine and oxaliplatin in advanced biliary tract cancer patients as well as multiple Phase 1 and Phase 2 clinical trials in China sponsored by TRACON’s corporate partners, Alphamab Oncology and 3D Medicines.

About ENVASARC (NCT04480502)

The ENVASARC pivotal trial is a multicenter, open label, randomized, non-comparative, parallel cohort study at 30 top cancer centers in the United States and the United Kingdom that began dosing in December 2020. TRACON expects the trial to enroll more than 160 patients with UPS or MFS who have progressed following one or two lines of prior treatment and have not received an immune checkpoint inhibitor, with 80 patients enrolled into a cohort of treatment with single agent envafolimab at 600 mg every three weeks and 80 patients enrolled into a cohort of treatment with envafolimab at 600 mg every three weeks with Yervoy. The primary endpoint is objective response rate by central review with duration of response a key secondary endpoint.

About YH001

YH001 is an IgG1 antibody against CTLA-4 that has shown enhanced antibody dependent cellular cytotoxicity and complement dependent cytotoxicity in vitro. In preclinical studies YH001 demonstrated superior T cell activation and superior tumor growth inhibition activity compared to ipilimumab. YH001 also demonstrated superior activity compared to ipilimumab in human transgenic mouse tumor models when combined with a PD-(L)1 antibody. In these models, single agent YH001 depleted regulatory T cells and increased CD8+ T cells in tumor tissue. YH001 is being studied with envafolimab and doxorubicin in a Phase 1/2 clinical trial sponsored by TRACON (NCT05448820), and in multiple Phase 1 trials in China and Australia sponsored by TRACON’s corporate partner Eucure, a division of Biocytogen.

About TRC102

TRC102 (methoxyamine) is a novel small molecule inhibitor of the DNA base excision repair pathway, which is a pathway that causes resistance to alkylating and antimetabolite chemotherapeutics. TRC102 is currently being studied in multiple Phase 1 and Phase 2 clinical trials sponsored by the National Cancer Institute through a Cooperative Research and Development Agreement (CRADA) and has orphan drug designation from the FDA in malignant glioma, including glioblastoma.

About TJ004309

TJ004309 is a novel, humanized antibody against CD73, an ecto-enzyme expressed on stromal cells and tumors that converts extracellular adenosine monophosphate to adenosine, which is highly immunosuppressive. TJ004309 is currently being studied in an ongoing Phase 1 trial to assess safety and preliminary efficacy as a single agent and when combined with the PD-L1 checkpoint inhibitor Tecentriq in patients with advanced solid tumors.

On November 14, 2022 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS’’ or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, reported important updates relating to its ongoing Phase 3 open-label registrational clinical trial (the REGAL study) for galinpepimut-S (GPS) in acute myeloid leukemia (AML) patients who have achieved complete remission following second-line salvage therapy (CR2 patients) (Press release, Sellas Life Sciences, NOV 14, 2022, View Source [SID1234624025]).

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The primary endpoint of the REGAL study is overall survival (OS). The trial was originally designed using certain assumptions regarding OS for both the GPS treatment arm and the control arm receiving best available treatment (BAT) which are reflected in the protocol and statistical analysis plan (SAP) for the study. A review of preliminary data to date, which was pooled (i.e., GPS arm plus control arm) and which remains blinded as to treatment arm, suggests that the median OS in the pooled study population is likely considerably longer, by approximately two-fold, than originally anticipated and upon which the SAP was based. Accordingly, the overall duration of the REGAL study is now expected to be longer than initially predicted.

Following consultation with members of the Independent Data Monitoring Committee for the REGAL study and AML key opinion leaders, as well as the recommendations of the Company’s biostatistics experts, SELLAS is implementing changes to the SAP and protocol for the REGAL study as follows:

The total targeted enrollment in the study will increase from 116 patients to a range of 125 to no more than 140 patients.
The targeted number of events (deaths) for the interim analysis will be reduced to 60 from 80 and is currently expected to occur in late 2023 or early 2024.
The targeted number of events (deaths) for the final analysis will be reduced to 80 from 105 and is currently expected to occur by the end of 2024.
Statistical significance would be achieved by an estimated hazard ratio (HR) for OS of 0.636, corresponding to an OS of 12.6 months versus eight months for GPS versus BAT, respectively.
The Company has developed these changes using a conservative application of the O’Brien-Fleming statistical theory, which is suitable when regulatory approval is expected to be based predominantly on results from a single clinical trial and when mortality is the primary endpoint. The Company has notified the U.S. Food and Drug Administration of these changes through a filing to the investigational new drug application (IND) for GPS.

Additionally, SELLAS’ development and commercialization partner for the Greater China territory, 3D Medicines (3DMed), has agreed to participate in the REGAL trial through the inclusion of approximately 20 patients from the Greater China territory. Such participation by 3DMed is possible due to the increase in the target patient enrollment in the study and will trigger significant milestone payments, which SELLAS expects to receive in the first half of 2023. If the REGAL study meets its primary endpoint for efficacy and the Chinese regulatory authorities determine that the REGAL data is sufficient for approval in China, GPS could potentially reach the market in Greater China much earlier than had been anticipated by SELLAS and 3DMed when the parties entered into the license agreement providing rights to 3DMed, triggering additional regulatory and commercialization milestones and royalties for SELLAS.

"The review of the pooled blinded dataset from the REGAL study shows that the entire trial population has a longer than originally expected OS duration," said Angelos Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS. "The causative reason for this result remains unknown and could be attributed to many factors, including the potential for, and extent of, increased clinical benefit accorded by the active GPS arm as well as an evolving treatment landscape and potentially better care for the patients receiving BAT. However, without unblinding the study, it is currently impossible to confirm or refute any of the possibilities. Upon examining the pooled blinded dataset, we worked expeditiously with our biostatisticians and other clinical advisors to refine our SAP, taking into account the observed longer OS, which has resulted in a reduction of the number of events needed for the interim and final analyses while maintaining a similar hazard ratio."

"Furthermore, our team has agreed on a path forward with our partner 3DMed to allow for 3DMed to participate in the REGAL trial and to enroll Chinese patients in a Phase 3 study much earlier than anticipated. This has been made possible by the refinements we are making for the REGAL study. Assuming a statistically significant and clinical beneficial outcome of the REGAL study, as well as agreement by the Chinese regulatory authorities that such data is sufficient for approval in China, GPS may become available to patients in China far earlier than originally thought, which would be a positive outcome for patients in need of better AML therapies," continued Dr. Stergiou.

Phase 3 REGAL Study Update Virtual Investor Event

SELLAS will hold a virtual investor event today, November 14, 2022, at 8:30 a.m. ET at which the Company will discuss these updates. The event will be facilitated by SELLAS management, including the Company’s President and CEO, Angelos Stergiou, MD, ScD h.c., and Dragan Cicic, MD, Senior Vice President, Clinical Development, who will be joined by leading cancer researcher, M. Yair Levy, M.D., Director of Hematologic Malignancies Research at the Baylor University Medical Center and member of the REGAL Steering Committee.

On November 14, 2022 Scholar Rock (NASDAQ: SRRK), a Phase 3 clinical-stage biopharmaceutical company focused on the treatment of serious diseases in which protein growth factors play a fundamental role, reported financial results and corporate updates for the third quarter ended September 30, 2022 (Press release, Scholar Rock, NOV 14, 2022, View Source [SID1234624024]).

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"We continue to build conviction in our clinical programs with recent TOPAZ data indicating apitegromab’s potential for sustained improvements of quality-of-life measures over 24 months, and with the most recently available SRK-181 data from DRAGON that we presented at SITC (Free SITC Whitepaper)," said Jay Backstrom, M.D., M.P.H., Chief Executive Officer & President of Scholar Rock. "I am excited to strengthen our experienced executive team with the addition of Scholar Rock’s new CMO, Dr. Jing Marantz. I am confident the continued momentum of the Phase 3 SAPPHIRE trial and the DRAGON trial will be further bolstered under her leadership."

Company Highlights and Upcoming Milestones

Pipeline Updates

Apitegromab is a selective inhibitor of myostatin activation being developed as the potential first muscle-targeted therapy for the treatment of spinal muscular atrophy (SMA).

Presented new Phase 2 TOPAZ trial data indicating positive trends in quality-of-life measures over 24 months with apitegromab for nonambulatory patients with Types 2 and 3 SMA. Scholar Rock presented these data, which indicate the potential for sustained improvement in quality-of-life measures for patients with symptomatic SMA and offer further signs of possible durable effects of apitegromab, at the World Muscle Society (WMS) Hybrid Congress and the International Scientific Congress on Spinal Muscular Atrophy in October.

Continued enrollment of the Phase 3 SAPPHIRE clinical trial. SAPPHIRE, a randomized, double-blind, placebo-controlled clinical trial evaluating apitegromab for patients with non-ambulatory Types 2 and 3 SMA on either nusinersen or risdiplam, is actively enrolling SMA patients across 55 sites in the U.S. and Europe. The anticipated enrollment is approximately 156 patients aged 2-12 in the main efficacy population.
SRK-181 is an investigational selective inhibitor of latent TGFβ1 activation and is being developed with the aim of overcoming resistance in patients with advanced cancer.

Data from the Phase 1 DRAGON trial presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s Annual Meeting show that SRK-181 continues to be generally well tolerated with early indications of efficacy (as of the data cut-off date of August 29, 2022).
No dose-limiting toxicities were observed in patients participating in Part A, and all dose levels were generally well tolerated, including the recommended SRK-181 dose of 1500 mg q3w or 1000 mg q2w in combination with anti‑PD-(L)1 for Part B.
In Part A2 of the trial (n=15), there was one confirmed partial response ("PR") in a patient with anti-PD-1 resistant clear cell renal cell carcinoma at 800mg who remained in the study for 30 weeks. Response was assessed based on RECIST 1.1 by principal investigators. One ongoing patient in the 2400 mg dose group of Part A2 with head and neck cancer experienced a 29.4% tumor reduction.
Enrollment in DRAGON Part B is ongoing. Across the cohorts, 14 patients have been dosed as of the data cut-off date. The recommended dose of 1500mg q3w or 1000mg q2w SRK-181 in combination with anti-PD-(L)1 was generally well tolerated. There was a confirmed PR in one ongoing patient with anti-PD-1 resistant clear cell renal cell carcinoma. Scholar Rock will continue to provide updates at future scientific meetings.
Corporate Updates

Announced key leadership appointments:
Jay Backstrom, M.D., M.P.H. was appointed President & CEO in October, bringing an exceptional range of research and development, regulatory, and leadership experience spanning several decades in the biopharmaceutical industry. He has been instrumental in organizing and executing development strategies and has led programs in a broad range of therapeutic areas through regulatory approvals. Dr. Backstrom most recently served as Executive Vice President, Research and Development at Acceleron Pharma, which was acquired by Merck in 2021.
Jing L. Marantz, M.D., Ph.D., M.B.A., was appointed Chief Medical Officer in November. Dr. Marantz is an accomplished biopharmaceutical executive with over 20 years of industry experience spanning multiple specialties, including neurology, hematology/oncology, and rare diseases. Most recently, she served as the Executive Vice President and Chief Business Officer at Krystal Biotech. Previously, she was Senior Vice President and Head of Medical Affairs at Acceleron Pharma, where she also was a member of the R&D leadership team.
Amended debt facility with Oxford Finance and Silicon Valley Bank. Scholar Rock amended the existing debt facility with Oxford Finance and Silicon Valley Bank. Under the agreement, an additional $25 million tranche is available at the company’s discretion and subject to meeting certain criteria. The amendment also extends both the interest-only period for an additional 24 months to November 2024, and the loan maturity date to November 2027.
Third Quarter 2022 Financial Results

For the quarter ended September 30, 2022, net loss was $43.3 million or $0.55 per share compared to a net loss of $37.5 million or $1.02 per share for the quarter ended September 30, 2021.

Revenue was $0 for the quarter ended September 30, 2022, compared to $5.5 million for the quarter ended September 30, 2021.
Research and development expense was $33.4 million for the quarter ended September 30, 2022, compared to $31.3 million for the quarter ended September 30, 2021. The increase was primarily attributable to expenses related to non-cash equity-based compensation expense, a component of employee compensation and benefits costs.
General and administrative expense was $10.5 million for the quarter ended September 30, 2022, compared to $11.3 million for the quarter ended September 30, 2021. The decrease was attributable to the reduction of employee severance and benefits expenses that were recognized during the same period in the prior year.
As of September 30, 2022, Scholar Rock had cash, cash equivalents, and marketable securities of approximately $343.7 million, which is expected to fund the Company’s anticipated operating and capital expenditure requirements into 2025.
"With the successful equity financing that we completed in the second quarter and the added flexibility provided by the amendment of our debt facility, we are well funded to advance our pipeline through key milestones," said Ted Myles, Chief Operating Officer and Chief Financial Officer of Scholar Rock. "We believe the company is well positioned to deliver value to patients with unmet medical needs. With sufficient capital to complete the topline data readout from the SAPPHIRE study, progress Part B of the DRAGON trial, and continue advancing select preclinical programs, we are laser focused on the successful execution of these priorities."