On May 26, 2022 Alpha Tau Medical Ltd. (NASDAQ: DRTS) (NASDAQ: DRTSW), ("Alpha Tau" or the "Company"), the developer of the innovative alpha-radiation cancer therapy Alpha DaRT, reported first quarter 2022 financial results and provided a corporate update (Press release, Alpha Tau Medical, MAY 26, 2022, View Source [SID1234615147]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"2022 is an important year for the Company, as we look to initiate a number of important clinical trials across large global markets, including our first U.S. pivotal trial as well as trials in internal organs such as the prostate," commented Alpha Tau CEO Uzi Sofer. "The first quarter of 2022 already saw us reach a number of meaningful milestones, including our first U.S. data read out and our debut as a public company traded on NASDAQ under symbol "DRTS." We are also working in parallel to expand our manufacturing capabilities and to strengthen our supply chain in the U.S., Israel, and Asia, as part of the expansion of our clinical trial activities and future commercialization."

First quarter 2022 Corporate Highlights:

Reported results in January 2022 from the first pilot multi-center study of Alpha DaRT in the United States, led by Memorial Sloan Kettering Cancer Center. In this trial of malignant skin and soft tissue cancer patients, a complete response, as measured by RECIST criteria, was observed in all ten out of ten tumors treated (100%), with no product-related serious adverse events reported. Alongside these data, a 98% overall response rate was observed in a pooled analysis of superficial tumors treated that reached their efficacy endpoint measurement by quarter end, across the Company’s various trials.
Completed patient recruitment in the Company’s Japanese pivotal trial in head and neck cancer, with data submission targeted for the second half of 2022.
Entered into a sponsored research agreement with investigators at The University of Texas MD Anderson Cancer Center in January 2022 to evaluate the combination of Alpha DaRT with DNA-repair inhibitors and immune checkpoint inhibitors for the treatment of breast tumors.
Completed its business combination in March 2022 with Healthcare Capital Corp., a special purpose acquisition company, together with a concurrent Private Investment in Public Equity (PIPE) financing, raising a total of approximately $104 million in gross proceeds, and commenced trading of its shares and warrants on the Nasdaq Capital Market under the symbols "DRTS" and "DRTSW", respectively.
Appointed Ruth (Ruti) Alon to its Board of Directors in March 2022. Ms. Alon brings a wealth of healthcare experience and serves on the boards of multiple private and public companies in the sector.
Upcoming 2022 Milestone Targets Include:

First Israeli patient in the prostate cancer feasibility trial in the second quarter of 2022.
Initiation of multi-center pivotal U.S. trial in skin cancers in the middle of 2022.
Recruitment in the Canadian feasibility trial in pancreatic tumors to begin in the second half of 2022.
Submission of Alpha DaRT pivotal trial in head and neck cancer to Japan’s PMDA in the second half of 2022 for marketing authorization.
Financial results for the first quarter ended March 31, 2022

R&D expenses for the quarter ended March 31, 2022 were $5.2 million, compared to $2.2 million for the same period in 2021, primarily due to increased R&D activity and increased share-based compensation costs.

Marketing expenses for the quarter ended March 31, 2022 were $0.2 million, compared to $0.2 million for the same period in 2021.

G&A expenses for the quarter ended March 31, 2022 were $3.3 million, compared to $0.4 million for the same period in 2021, primarily due to costs associated with the merger with Healthcare Capital Corp., increased professional fees and share-based compensation.

Financial expenses, net, for the quarter ended March 31, 2022 were $17.0 million, compared to $9.0 million for the same period in 2021, primarily due to an increase in the revaluation of warrants.

For the quarter ended March 31, 2022, the Company had a net loss of $25.7 million, or ($0.54) per share, compared to a loss of $11.7 million, or ($0.29) per share, in the same period in 2021.

Balance Sheet Highlights

As of March 31, 2022, the Company had cash and cash equivalents, restricted cash and short term deposits in the amount of $107.0 million, compared to $31.9 million on December 31, 2021. In addition, incremental proceeds of approximately $13 million from the original PIPE were received after March 31, 2022. The Company expects that this cash balance will be sufficient to fund operations for at least two years.

In addition, the Company’s Board of Directors approved a program for the buyback of the Company’s publicly traded warrants in an amount of up to $3 million. Repurchases may be started or suspended at any time without prior notice, depending on market conditions and other factors.

About Alpha DaRT

Alpha DaRT (Diffusing Alpha-emitters Radiation Therapy) is designed to enable highly potent and conformal alpha-irradiation of solid tumors by intratumoral insertion of radium-224 impregnated seeds. When the radium decays, its short-lived daughters are released from the seed, and disperse while emitting high-energy alpha particles with the goal of destroying the tumor. Since the alpha-emitting atoms diffuse only a short distance, Alpha DaRT aims to mainly affect the tumor, and to spare the healthy tissue around it.

On May 26, 2022 Leap Therapeutics, Inc. (Nasdaq: LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported that initial clinical data from the investigator-sponsored Phase 1b/2a dose escalation and dose expansion study testing Leap’s anti-Dickkopf-1 (DKK1) antibody, DKN-01, as monotherapy or in combination with docetaxel in metastatic castration-resistant prostate cancer (mCRPC) will be presented at the upcoming 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place in Chicago, IL on June 3-7, 2022 (Press release, Leap Therapeutics, MAY 26, 2022, View Source [SID1234615146]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"As the initial data show, DKN-01 in combination with docetaxel is a promising therapy option for prostate cancer patients, particularly for those with aggressive variant prostate cancer," said David Wise, MD, PhD, Medical Oncologist at Perlmutter Cancer Center, NYU Langone Health and principal investigator on the study. "DKN-01, as a monotherapy and in combination with docetaxel, was well tolerated by patients, with partial responses in all of the patients treated with DKN-01 in combination with docetaxel who had measurable disease. Accrual into the Phase 2 portion of this study is ongoing, alongside preclinical and correlative studies aiming to further investigate the mechanism of action of DKN-01 in prostate cancer and to identify the best clinical path forward."

Key Initial Findings from the Investigator-Sponsored Phase 1b/2a Clinical Trial:

Data that will be presented at ASCO (Free ASCO Whitepaper) is from the completed Phase 1 portion of the study. Thirteen patients were enrolled, with 7 patients in the DKN-01 monotherapy cohort and 6 patients in the DKN-01 plus docetaxel combination cohort. The primary endpoint of the Phase 1 dose escalation cohorts was safety, characterized by dose-limiting toxicity (DLT). The study also aims to study correlations between DKK1 expression and tumor genetics, histology and anti-tumor activity.

Highlights from the data include:

No DLTs were observed at DKN-01 300mg or 600mg dose levels as monotherapy or in combination with docetaxel, and no treatment-related adverse events occurred in either cohort
No partial responses (PR) were seen in the monotherapy cohort with best overall response of stable disease in 2 out of 5 evaluable patients
In the combination cohort, all 5 evaluable patients had a PR as measured by RECIST (3 confirmed, 2 unconfirmed) and by PSA50
Confirmed partial responses in the combination cohort were observed in both DKK1 high and low expressing tumors, including in 2 out of 3 patients with aggressive variant prostate cancer (AVPC)
Further accrual into the phase 2 part of this study is ongoing, alongside preclinical and correlative studies aimed at investigating the mechanism of action of DKN-01 in prostate cancer.

On May 26, 2022 Protagonist Therapeutics (Nasdaq: PTGX) reported new data from its ongoing Phase 2 REVIVE study evaluating rusfertide in patients with polycythemia vera (PV) (Press release, Protagonist, MAY 26, 2022, View Source [SID1234615145]). These results will be shared as an oral presentation at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, being held in Chicago from June 3-7, 2022.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are pleased to observe that administration of rusfertide continues to provide PV patients with an effective therapy that leads to rapid and sustained hematocrit control, and potentially offers patients a better quality of life by keeping them essentially phlebotomy-free for up to 18 months," said Ronald Hoffman, M.D., Director of the Myeloproliferative Disorders Research Program at the Icahn School of Medicine at Mount Sinai and principal investigator of the REVIVE study. "Importantly, the new results show that rusfertide administration suspension, due to the brief clinical hold, directly led to increases in hematocrit levels, red blood cell counts, and phlebotomy rates. In contrast, resumption of rusfertide quickly restored the therapeutic benefits for patients, confirming the direct and rapid effect of rusfertide and its potential utility in treating this serious disease."

"These highly promising new results continue to demonstrate the rapid therapeutic effect of rusfertide and its utility as an effective potential treatment across all categories of PV patients, independent of patient risk category, or concurrent therapy with other cytoreductive treatments including hydroxyurea, interferons or JAK inhibitors," said Dinesh V. Patel, Ph.D., President and Chief Executive Officer of Protagonist. "Taken together, these data reaffirm our belief in the potential of rusfertide to provide a highly effective treatment option for patients with PV, providing an opportunity to fundamentally transform the management of this disease. Rusfertide continues to be the primary focus of our corporate resources and efforts, and we continue to explore the full therapeutic potential of rusfertide with a sharp focus on the execution of the recently initiated Phase 3 VERIFY study."

Summary of Key Results

Updated Results from Phase 2 Studies Evaluating Rusfertide in Patients with PV

REVIVE Study

The ongoing Phase 2 REVIVE study was designed to evaluate rusfertide in patients with phlebotomy-dependent PV for up to 18 months. Results from the 70 phlebotomy-dependent PV patients continued to demonstrate that rusfertide treatment essentially eliminated the need for therapeutic phlebotomy (TP), and led to rapid, sustained, and durable control of hematocrit (HCT) levels below 45% without a clinically meaningful increase in white blood cell numbers of PV-related thromboses. Rusfertide treatment also led to normalization of iron stores and improved symptoms including concentration.

Furthermore, the new data showed that treatment suspension in PV patients led to increases in hematocrit levels, RBC count, and phlebotomy rates. In contrast, resumption of rusfertide treatment in those patients led to significant improvement in those parameters, providing further evidence of the rapid and beneficial therapeutic effect of rusfertide in PV. Upon the lifting of the clinical hold placed on rusfertide in PV, about 85% of patients resumed treatment with rusfertide.

PACIFIC Study

The ongoing Phase 2 PACIFIC study enrolled 20 patients with confirmed high HCT levels above 48% to evaluate rusfertide as an induction therapy. Results demonstrated that all erythrocytotic PV patients on rusfertide induction therapy with twice weekly dosing achieved rapid, sustained and durable HCT control below 45%, and without the need for TP.

Details for the ASCO (Free ASCO Whitepaper) 2022 oral presentation are as follows:

Title: Rusfertide (PTG-300) treatment in phlebotomy-dependent polycythemia vera patients.
Authors: Ronald Hoffman, M.D., The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, Protagonist Therapeutics
Abstract Number: #7003
Session: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant
Presentation Date and Time: June 7, 2022 at 10:45 a.m. CT

About Rusfertide

Rusfertide (PTG-300) is an investigational, injectable hepcidin mimetic that is currently being developed for various disorders associated with iron overload and/or excessive erythrocytosis (red blood cell production). Rusfertide regulates iron homeostasis and controls the absorption, storage, and distribution of iron in the body. Discovered through Protagonist’s peptide technology platform, rusfertide is currently being investigated in the REVIVE Phase 2 proof-of-concept clinical trial for polycythemia vera (PV), a rare chronic blood disorder that affects about 160,000 patients in the U.S., the PACIFIC Phase 2 study in PV subjects with high hematocrit levels, and a recently completed Phase 2a study for hereditary hemochromatosis. The VERIFY Phase 3 study is currently underway.

On May 26, 2022 I-Mab (the "Company") (Nasdaq" IMAB), a clinical-stage biopharmaceutical company committed to the discovery, development and commercialization of novel biologics, reported preliminary data of its ongoing Phase 2 clinical trial (NCT04322006) with uliledlimab (also known as TJD5, or TJ004309), a differentiated CD73 antibody, and its global clinical development plan (Press release, I-Mab Biopharma, MAY 26, 2022, View Source [SID1234615144]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

At the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, preliminary results through December 2021 from an ongoing Phase 2 clinical study of uliledlimab in combination with toripalimab (TUOYI) in patients with non-small cell lung cancer (NSCLC) were released.[1] These results were largely consistent with those observed in Phase 1 clinical trial in relation to favorable drug safety and pharmacokinetics (PK) and pharmacodynamic (PD) profile of ulilelimab. Uliledlimab appears safe and well-tolerated up to the highest doses tested at 30 mg/kg Q3W, as a monotherapy and a combination therapy with toripalimab with no dose limiting toxicity (DLT). Uliledlimab exhibited a linear PK profile at doses ≥5mg/kg and a dose-dependent receptor occupancy with no "hook effect", where the antibody loses its effectiveness at high concentrations.

The most updated Phase 2 data are summarized as follows with the new data cutoff of March 29, 2022. Among three NSCLC patient cohorts who were under different treatment settings, clinical response varied. The highest response rates were observed in the patient cohort with advanced NSCLC (mostly stage 4 disease) who were previously ineligible for standard of care, while the other two cohorts with advanced NSCLC who were heavily treated showed a lower clinical response. Among 19 efficacy evaluable patients from this cohort, 5 partial responses (5 PR, overall response rate [ORR]=26%) and 9 stable disease (9 SD, disease control rate [DCR] =73.7%) were observed. Approximately 80% patients in this cohort showed low PD-L1 expression in baseline tumor samples (tumor proportion score [TPS] 1-49% or TPS<1%) who were considered less responsive to a checkpoint inhibitor therapy as demonstrated in KEYNOTE-042 (ORR=16.9% for patient with PD-L1 TPS 1-49%)[2]. Noticeably, the clinical response observed in this patient cohort displayed a correlation with CD73 expression in tumors. High CD73 expression (≥35% expression level in tumor cells or immune cells) was found in 4/5 PRs with a mean value of 53.4%, 4/9 SDs with a mean value of 30.5% and none in the 5 remaining patients with a mean value of 19.2% who progressed on the treatment. The clinical data continue to mature.

"The data represent a step forward for advanced non-small-cell lung cancer patients. To date, uliledlimab has shown a favorable safety profile and positive anti-tumor activity in lung cancer patients, particularly in those patients with a higher baseline CD73 expression," said Professor Yi-Long Wu, Principal Investigator of the study and Professor of Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences and Guangdong Lung Cancer Institute. "While the study is ongoing and we are analyzing the data as they mature, we are extremely encouraged by these results and the clinical benefits that uliledlimab may offer to cancer patients."

This Phase 2 clinical trial is still ongoing with patients on-study for continued treatment and follow-up evaluation. The Company plans to expand the study with the aim to focus on the selected NSCLC patient cohort for further evaluation of treatment efficacy as well as the role of CD73 as a potential predictive biomarker. The future clinical development plan of uliledlimab includes a Phase 3 registrational clinical trial in patients with NSCLC to be expected next year if approved by the China National Medical Products Administration and another clinical trial in the United States in other selected cancer types and beyond combination with PD-1/PD-L1 therapy in the next 12 months.

"The latest data readout, although preliminary, gives hope to those lung cancer patients who often do not benefit from the currently available treatments," said Dr. Andrew Zhu, President of I-Mab. "We are excited by uliledlimab’s potential as a best-in-class CD73 antibody and the clinical results obtained so far have given us the confidence for further clinical development towards registration. We look forward to accelerating our clinical development plan in China and the U.S. with the goal to initiate a registrational clinical study soon."

Uliledlimab is a differentiated CD73 antibody that is designed to avoid a "hook effect" seen in other clinical stage CD73 antibodies. This differentiated property is enabled through uliledlimab’s novel C-terminus epitope and its associated intra-dimer binding mode, leading to a favorable PK and PD relationship as confirmed in both Phase 1 and the ongoing Phase 2 clinical trials.

In a Phase 1 clinical trial of uliledlimab in combination with atezolizumab (Tecentriq), uliledlimab was well tolerated with encouraging efficacy signals in heavily treated cancer patients (ORR=23%, DCR=46%) as presented at ASCO (Free ASCO Whitepaper) 2021[3]. Recommended Phase 2 dose (RP2D) was determined at 20 mg/kg, Q3W and there was a potential correlation between high tumoral expression of CD73 and the observed clinical response.

The Company will host an investor conference call to provide an in-depth clinical data analysis at 8 a.m. Eastern Time on May 27, 2022. Details for the conference call are as follows:

About Uliledlimab (TJD5)

Uliledlimab (TJD5) is a differentiated, humanized antibody against CD73, an ecto-enzyme expressed on stromal cells and tumors that converts extracellular adenosine monophosphate (AMP) to adenosine. Adenosine in turn binds to adenosine receptors on relevant immune cells and inhibits anti-tumor immune responses in tumor microenvironment. Uliledlimab is expected to offer clinical benefit by suppressing tumor growth in concert with checkpoint therapies such as PD-(L)1 antibodies. Uliledlimab is effective in anti-tumor activities through a unique intra-dimer binding, leading to differentiated and favorable functional properties as evident in preclinical studies.

On May 26, 2022 Gracell Biotechnologies Inc. ("Gracell" or the "Company",NASDAQ: GRCL), a global clinical-stage biopharmaceutical company dedicated to developing highly efficacious and affordable cell therapies for the treatment of cancer, reported that it will present updated clinical data from a multicenter investigator-initiated trial (IIT) evaluating GC012F, the company’s B-cell maturation antigen (BCMA) and CD19 dual-targeting CAR-T candidate, for the treatment of relapsed/refractory multiple myeloma (RRMM) in an oral abstract presentation at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (ASCO 2022) Annual Meeting (Press release, Gracell Biotechnologies, MAY 26, 2022, View Source [SID1234615143]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

GC012F is an autologous CAR-T therapeutic candidate dual-targeting BCMA and CD19, developed using Gracell’s proprietary FasTCAR platform, which enables next-day manufacturing of CAR-T therapies. In November 2021, GC012F was granted Orphan Drug Designation for the treatment of multiple myeloma (MM) by the U.S. Food and Drug Administration. GC012F is currently being evaluated in IITs in China including in MM and B-NHL.

"We are thrilled to present updated data from our ongoing study of GC012F for the treatment of patients with RRMM at the oral abstract session at ASCO (Free ASCO Whitepaper)," said Dr. Martina A. Sersch, Chief Medical Officer of Gracell. "GC012F is the first dual-targeting CAR-T with clinical data in RRMM, which is designed to improve depth of response as well as tackling some of the major challenges of CAR-T therapy, including the need for faster delivery to the patients in need . We have followed patients for over two and a half years and also enrolled new patients into the study. RRMM still remains an area of unmet medical need, including the need of deepening responses for eligible patients."

From October 2019 to November 2021, 28 heavily pretreated RRMM patients were enrolled and treated in this single-arm, open label, multicenter IIT with a single infusion of GC012F at three dose levels: 1×105 cells/kg (DL1), 2×105 cells/kg (DL2), and 3×105 cells/kg (DL3). An additional 9 patients were treated in three different dose levels since the last update reported at ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper) in 2021. 89.3% (25/28) patients were high risk based on mSMART 3.0 criteria and patients had received a median of five prior lines of therapy.

At the data cutoff of January 26, 2022, the 28 patients had been evaluated for response with a median follow-up time of 6.3 months, ranging from 1.8 to 29.9 months. Patients are continued to be followed for deepening responses. The response rate at different dose levels was 100% (2/2) in DL1, 80% (8/10) in DL2, and 93.8% (15/16) in DL3. All (27/27, 100%) MRD-assessable patients achieved minimal residual disease (MRD) negativity. 75% (21/28) of all patients treated achieved MRD- sCR.

The safety profile of GC012F was consistent with previous findings with mostly low grade of cytokine release syndrome (CRS) (Grade 0-2 (93%)). No Grade 4 or 5 CRS, or any Grade immune effector cell-associated neurotoxicity syndrome (ICANS) were observed. Patients continue to be monitored for safety and efficacy including best overall response and duration of response.

Gracell will also present as an oral abstract presentation the updated results from this IIT evaluating GC012F for the treatment of RRMM patients at the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Hybrid Congress. For more information on the study, please visit ClinicalTrials.gov using the identifier: NCT04236011.

Details of the ASCO (Free ASCO Whitepaper) presentation follow below:

2022 ASCO (Free ASCO Whitepaper) Annual Meeting

Abstract title: Updated results of a multicenter first-in-human study of BCMA/CD19 dual-targeting FasTCAR-T GC012F for patients with relapsed/refractory multiple myeloma (RRMM)
Abstract number: 8005
Session title: Hematologic Malignancies – Plasma Cell Dyscrasia
Presentation time: Sunday, June 5 at 9:36 AM CT
Presentation location: S406
About GC012F

GC012F is a FasTCAR-enabled dual-targeting CAR-T product candidate that is currently being evaluated in IIT studies in China for the treatment of multiple myeloma and B-cell non-Hodgkin’s lymphoma. GC012F simultaneously targets CD19 and BCMA to drive fast, deep and durable responses, which can potentially improve efficacy and reduce relapse in multiple myeloma and B-NHL patients.

About FasTCAR

CAR-T cells manufactured on Gracell’s proprietary FasTCAR platform appear younger, less exhausted and show enhanced proliferation, persistence, bone marrow migration and tumor cell clearance activities as demonstrated in preclinical studies. With next-day manufacturing, FasTCAR is able to significantly improve cell production efficiency which may result in meaningful cost savings, and, together with fast turnaround time, enables enhanced accessibility of cell therapies for cancer patients.