On August 15, 2022 Inhibrx, Inc. (Nasdaq: INBX), a biotechnology company with four clinical programs in development and a strong emerging pipeline, reported that the European Commission ("EC"), based on a positive opinion issued by the European Medicines Agency ("EMA"), has granted orphan medicinal product designation to INBRX-109 for the treatment of chondrosarcoma (Press release, Inhibrx, AUG 15, 2022, View Source [SID1234618350]).

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"We are highly optimistic about the potential of INBRX-109 in chondrosarcoma to address a high unmet medical need," said Inhibrx Chief Executive Officer, Mark Lappe. "The positive opinion issued by the EMA is excellent news and acknowledges the potential of INBRX-109 as a treatment for patients throughout Europe who suffer from this debilitating, rare condition."
The EC grants orphan designation to drugs and biologics intended for the safe and effective treatment, prevention, or diagnosis of a disease that is life-threatening or chronically debilitating impacting fewer than five in 10,000 patients in the European Union ("EU"). Orphan drug designation in the EU can provide certain benefits, including reduced regulatory fees, clinical protocol assistance and the potential for up to ten years of market exclusivity following regulatory approval.

About Chondrosarcoma

Chondrosarcoma is an orphan bone cancer with approximately 2,800 new patients diagnosed annually in the United States and the EU. There are currently no therapeutics approved for the treatment of chondrosarcoma.

About INBRX-109

INBRX-109 is a precision-engineered, tetravalent death receptor 5 (DR5) agonist antibody designed to exploit the tumor-biased cell death induced by DR5 activation.

In 2021, the FDA granted Fast Track designation to INBRX-109 for the treatment of patients with unresectable or metastatic conventional chondrosarcoma and orphan-drug designation to INBRX-109 for chondrosarcoma in the United States.

In June 2021, Inhibrx initiated a randomized, blinded, placebo-controlled, potential registration-enabling Phase 2 trial of INBRX-109 in conventional chondrosarcoma, which is currently ongoing.

In November 2021, Inhibrx provided updated results from its ongoing Phase 1 clinical trial evaluating the efficacy and safety of INBRX-109 in patients with conventional chondrosarcoma. Preliminary disease control was observed in 16 of the 18 evaluable patients (89%) measured by

RECISTv1.1, with two of the 18 achieving partial responses (11%). Based on preliminary results of the ongoing Phase 1 trial at that time, the median progression-free survival (PFS) was 7.4 months, and the median overall survival had not been reached. Three patients had exceeded 61 weeks on treatment with INBRX-109, with 77 weeks being the longest duration of stable disease observed at that time.

On August 15, 2022 VBL Therapeutics (Nasdaq: VBLT), a biotechnology company developing targeted medicines for immune-inflammatory diseases, reported financial results for the second quarter ended June 30, 2022 and provided a corporate update (Press release, VBL Therapeutics, AUG 15, 2022, View Source [SID1234618349]).

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"Following our announcement in July that the Phase 3 OVAL trial evaluating ofra-vec did not meet its primary endpoints, we began an internal strategic review of our development programs with the goal of maximizing shareholder value," said Dror Harats, M.D., Chief Executive Officer of VBL. "We have taken steps to preserve capital, including the workforce reduction announced earlier in August and ceasing development of ofra-vec in all indications. We see opportunities to create value from our assets including from our Monocyte Targeting Technology (MTT), which offers a novel and differentiated approach to targeting inflammation and our gene therapy manufacturing facility. Our VB-601 program, the first candidate from the MTT program, remains on track and we plan to enter the clinic with this program in the fourth quarter of 2022."

In August 2022, VBL retained Chardan to act as its financial advisor to explore and evaluate strategic options for maximizing shareholder value. Strategic alternatives that may be explored or evaluated as part of this process include the potential for an acquisition, merger, business combination or other strategic transaction or transactions involving VBL. VBL’s board of directors has not set a timetable for the conclusion of this review, nor has it made any decisions related to any further actions or potential strategic options at this time. There can be no assurance, however, that this process will result in any such transaction.

Financial Results for the Second Quarter of 2022

At June 30, 2022, VBL had cash, cash equivalents, short-term bank deposits and restricted bank deposits of $34.5 million. VBL expects that its cash, cash equivalents, short-term bank deposits, and restricted bank deposits will be sufficient to fund currently planned operating expenses and capital expenditures for at least the next 12 months. VBL’s review of its strategic options and any transaction resulting from such review may impact this projection.
For the quarter ended June 30, 2022, VBL reported a net loss of $9.4 million, or ($0.12) per basic share, compared to a net loss of $8.0 million, or ($0.12) per basic share, in the comparable period in 2021.
For the quarter ended June 30, 2022, total operating expenses were approximately $9.6 million, consisting of $6.7 million in research and development expenses, net, and $2.9 million in general and administrative expenses. This compares with total operating expenses of $8.0 million in the second quarter ended June 30, 2021, which was comprised of $6.6 million in research and development expenses, net, and $1.5 million in general and administrative expenses.
Subsequent to the end of the second quarter, VBL announced that the OVAL phase 3 study did not meet either primary endpoint. VBL evaluated these subsequent events and determined that no adjustments to the June 30, 2022 financial statements were required as they were not known or expected as of that date. As the results are considered a triggering event, VBL will perform an impairment test on all of its long-lived assets in the third quarter of 2022 that may result in an impairment charge on such assets and potential new liabilities arising from the triggering event.

On August 15, 2022 Ayala Pharmaceuticals, Inc. (Nasdaq: AYLA), a clinical-stage oncology company focused on developing and commercializing small molecule therapeutics for patients suffering from rare and aggressive cancers, primarily in genetically defined patient populations, reported second-quarter 2022 financial results and provided a corporate update (Press release, Ayala Pharmaceuticals, AUG 15, 2022, View Source [SID1234618348]).

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"We continue to make considerable progress across our pipeline, and we were particularly excited to announce interim results from the ongoing Phase 2/3 RINGSIDE trial evaluating AL102 in desmoid tumors. Although early, the results showed substantial initial anti-tumor activity and a favorable side effect profile," said Roni Mamluk, Ph.D., Chief Executive Officer of Ayala. "Based on these positive results, our efforts are focused on finalizing the Part A of the study shortly followed by immediate initiation of Part B. For AL101, we were pleased with the latest interim results from the ACCURACY trial presented at ASCO (Free ASCO Whitepaper), which demonstrated anti-tumor monotherapy activity and evidence of improved progression-free survival (PFS) in patients with recurrent/metastatic ACC."

Second-quarter 2022 and Recent Business Highlights

In July, announced positive interim data from Part A of the Phase 2/3 RINGSIDE study of AL102 in desmoid tumors: Data showed tumor shrinkage in substantially all patients who were evaluable at 16 weeks. AL102 was well tolerated at all three dosing regimens with no dose-limiting toxicities and no Grade 4/5 adverse events. The results from Part A will be used to determine the dose of AL102 to be evaluated in Part B of RINGSIDE, the randomized portion of the study, which Ayala is on track to initiate in 3Q 2022. More advanced and comprehensive data from RINGSIDE is expected to be presented at ESMO (Free ESMO Whitepaper).
Data on AL101 in adenoid cystic carcinoma (ACC) presented at ASCO (Free ASCO Whitepaper) 2022 Annual Meeting: In a poster at ASCO (Free ASCO Whitepaper), the company provided an update from the 4mg and 6 mg AL101 cohorts in the ACCURACY study of AL101, a selective gamma-secretase inhibitor, in subjects with recurrent/metastatic (R/M) adenoid cystic carcinoma (ACC) harboring Notch activating mutations. An overall disease control rate of 66.7% was observed. The median PFS in each of the 4mg and 6mg dose cohorts was 3.7 months and 6.7 months among the patients who had a partial response.
Upcoming Milestones

More advanced data from the RINGSIDE trial in desmoid tumors: Ayala expects to present a more comprehensive data set from Part A of the RINGSIDE trial of AL102 at ESMO (Free ESMO Whitepaper).
Initiation of Part B of the RINGSIDE trial: Part B will be a double-blind placebo-controlled study enrolling up to 156 patients with progressive disease, randomized between AL102 or placebo. The primary endpoint will be PFS with secondary endpoints including objective response rates, duration of response, and patient-reported quality of life measures.
Initiate Phase 2 clinical trial evaluating AL102 in T-cell acute lymphoblastic leukemia (T-ALL): Ayala plans to begin an investigator-initiated Phase 2 clinical trial evaluating AL102 in R/R T-ALL around year-end.
Second-Quarter 2022 Financial Results

Cash Position: Cash and cash equivalents were $20.1 million as of June 30, 2022.

Collaboration Revenue: Collaboration revenue was $38 thousand for the second quarter of 2022, as compared to $761 thousand for the corresponding quarter in 2021.

R&D Expenses: Research and development expenses were $5.6 million for the second quarter of 2022, compared to $8.1 million for the corresponding quarter in 2021. The decrease is mainly due to the winding down of the ACCURACY study.

G&A Expenses: General and administrative expenses were $2.3 million for the second quarter of 2022, compared to $2.5 million for the second quarter of 2021.

Net Loss: Net loss was $8.2 million for the second quarter of 2022, resulting in basic and diluted net loss per share of $0.54. This compares with a net loss of $10.8 million for the second quarter of 2021 or basic and diluted net loss per share of $0.75 for that quarter.

For further details on the company’s financial results, refer to form Quarterly Report on Form 10-Q for the three months ended June 30, 2022, filed with the SEC on August 15, 2022.

On August 15, 2022 Calithera Biosciences, Inc. (Nasdaq: CALA), a clinical-stage, precision-oncology biopharmaceutical company, reported its financial results for the second quarter ended June 30, 2022 (Press release, Calithera Biosciences, AUG 15, 2022, View Source,the%20same%20period%20prior%20year. [SID1234618347]).

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"We continue to deliver on our commitment to efficiently advance our clinical programs, successfully initiating two new clinical trials and sharing program updates at two important medical conferences," said Susan Molineaux, PhD, president and chief executive officer of Calithera. "We look forward to sharing data from the ongoing mivavotinib and sapanisertib phase 2 trials by the first quarter of 2023, as well as providing an update on the progress of our preclinical synthetic lethality VPS4 program by the end of 2022."

Second Quarter 2022 and Other Recent Highlights

Initiated patient enrollment in phase 2 trial evaluating mivavotinib (SYK inhibitor) in r/r non-GCB DLBCL. In June, Calithera announced enrollment of the first patient in a multicenter phase 2 clinical trial (NCT05319028) evaluating the spleen tyrosine kinase (SYK) inhibitor mivavotinib (CB-659) in patients with relapsed/refractory non-germinal center B-cell like (non-GCB) diffuse large B-cell lymphoma (DLBCL), a DLBCL subpopulation that primarily comprises patients with activated B-cell like disease (ABC). The main study objectives are to confirm previously seen single-agent activity in non-GCB DLBCL patients, evaluate activity according to MYD88/CD79b mutational status, and refine dose/schedule in this patient population. The primary endpoints of the study are overall response rate as assessed by an independent radiology review committee and safety. Mivavotinib has the potential to be the first treatment specifically for non-GCB DLBCL, a population of patients with a historically poorer prognosis and therefore high unmet need, and potential to be the first treatment for a genetically-defined subset of ABC in patients with MyD88/CD79 mutations. Approximately 50% of all ABC DLBCL tumors have one or both of these mutations. Data from the ongoing phase 2 trial could position Calithera to initiate a study with registrational intent in biomarker-specific DLBCL populations. Calithera plans to share data from this trial by the first quarter of 2023.

In July, Calithera presented a trial-in-progress poster at the Pan Pacific Lymphoma Conference detailing the design of this phase 2 study.
Initiated patient enrollment in phase 2 trial sapanisertib (dual mTORC 1/2 inhibitor) in sqNSCLC. In July, Calithera announced enrollment of the first patient in a phase 2 clinical trial (NCT05275673) of the dual mTORC 1/2 inhibitor sapanisertib (CB-228) in patients with relapsed/refractory NRF2 (NFE2L2)-mutated squamous non-small cell lung cancer (sqNSCLC). The study is designed to confirm the selective activity of sapanisertib in NRF2-mutated tumors compared to wild-type tumors, and to refine dose in this biomarker-defined population. The primary endpoints of the study are investigator-assessed overall response rate (ORR) per RECIST v1.1, and safety. Data from this study could position Calithera to initiate a study with registrational intent in biomarker-specific sqNSCLC populations. Calithera plans to share data from this trial by the first quarter of 2023.

Announced presentation of phase 1/2 data from sapanisertib/telaglenastat combination study. In a mini oral session at the International Association for the Study of Lung Cancer (IASLC) 2022 World Conference on Lung Cancer (WCLC), Jonathan W. Riess, MD, MS, director of Thoracic Oncology and associate professor at UC Davis Comprehensive Cancer Center, presented dose-escalation findings from a multi-center phase 1/2 investigator-initiated study evaluating sapanisertib in combination with telaglenastat, an investigational glutaminase inhibitor, in biomarker-defined cohorts of patients with advanced non-small cell lung cancer (NSCLC). After evaluating five combination dosing levels in 13 patients, researchers determined that the sapanisertib/telaglenastat combination has a favorable tolerability profile at the recommended expansion dose. Early evidence of clinical benefit was observed in the dose-escalation cohort, including a partial response in a patient with NRF2-mutant squamous NSCLC and stable disease in a patient with KEAP1/NRF2-mutant adenosquamous NSCLC. As a next step, study investigators plan to enroll patients into one of four expansion cohorts evaluating sapanisertib plus telaglenastat in squamous NSCLC with and without NRF2 or KEAP1 mutations, and adenocarcinoma NSCLC with KRAS and KEAP1 or NRF2 mutations.

Continued to advance VPS4 program through lead optimization. Calithera previously announced internal discovery of a novel series of small-molecule inhibitors of vacuolar protein sorting-associated protein 4A (VPS4A) and VPS4B, as well as the presentation of data validating the synthetic-lethal interaction between the gene paralogs at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2022 Annual Meeting. Calithera believes these VPS4 inhibitors are the first active, on-target inhibitors of VPS4. Potent, selective, and pharmacologically active VPS4 inhibitors are expected to be well-tolerated and have strong single-agent activity in tumors with these mutations. Calithera continues to advance multiple VPS4 series through lead optimization and plans to share updates on this program by the end of the year.
Selected Second Quarter 2022 Financial Results

Cash and cash equivalents totaled $41.8 million at June 30, 2022.

Research and development expenses for the second quarter 2022 were $7.8 million, compared to $12.8 million in the same period prior year. The decrease of $5.0 million was primarily due to decreases in the telaglenastat and CB-280 programs, partially offset by increases in the sapanisertib and mivavotinub programs.

General and administrative expenses for the second quarter 2022 were $3.6 million, compared to $4.5 million in the same period prior year. The decrease of $0.9 million was primarily due to decreased personnel-related costs.

Other income, net for the second quarter 2022 was $2.3 million, compared to other expense of $4,000 in the same period prior year, primarily attributable to the decrease in fair value of warrant liabilities.

Net loss was $9.1 million for the three months ended June 30, 2022.

Conference Call Information

Calithera will host an update conference call today, Monday, August 15, at 2:00 p.m. Pacific Time/5:00 p.m. Eastern Time. To register for dial-in access to the call, please use this link. To access the live audio webcast or the subsequent archived recording, visit the Investors section of the Calithera website at www.calithera.com. The webcast will be recorded and available for replay on Calithera’s website for 30 days.

On August 15, 2022 Gritstone bio, Inc. (Nasdaq: GRTS), a clinical-stage biotechnology company that aims to develop the world’s most potent vaccines, reported that interim results from the Phase 1/2 trial of GRANITE, its individualized, vaccine-based immunotherapy candidate for solid tumor cancers, were published today in Nature Medicine (Press release, Gritstone Oncology, AUG 15, 2022, View Source [SID1234618346]). The paper, "Individualized, heterologous chimpanzee adenovirus and self-amplifying mRNA neoantigen vaccine for advanced metastatic solid tumors: phase 1 trial interim results," details results demonstrating that GRANITE generated strong, persistent, and functional tumor-specific CD4+ and CD8+ T cell responses that have potential broad applicability across a range of disease settings. The published data were originally presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2021, and acted as the basis for launching two randomized, controlled studies of GRANITE, including a Phase 2/3 trial that has registrational intent (GRANITE-CRC-1L).

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"The publication of this study in Nature Medicine emphasizes the importance, novelty and potential clinical value of the GRANITE program, and reinforces our foundational hypothesis that targeting multiple neoantigens based on each individual tumor’s mutations could drive meaningful clinical benefit, including extended overall survival," said Andrew Allen, M.D., Ph.D., Co-founder, President, and Chief Executive Officer of Gritstone. "Now we are advancing GRANITE into earlier disease settings, where immune responses are likely stronger, and patients generally have more time for immune destruction of tumors to take effect."

Since initiation of the Phase 1/2 study, Gritstone has followed study participants and observed increased overall survival (OS) in colorectal cancer (CRC) patients who demonstrated a molecular response (measured by a reduction in circulating tumor DNA [ctDNA] levels from baseline) versus those who did not. As of May 2022, median OS of this subgroup (treated third-line CRC patients who demonstrated a molecular response) exceeded 18 months with the median not yet reached. This compares to median OS of 7.8 months for patients who did not demonstrate a molecular response, results which are generally consistent with extensive prior data from patients receiving various third-line therapies. Baseline characteristics of these two patient populations are similar. The Phase 1/2 study remains ongoing.

"Personalized neoantigen immunotherapy is a rational approach to treating solid tumor cancers given the abundant evidence that T cells can recognize neoantigens and drive tumor destruction," said Karin Jooss, Ph.D., Executive Vice President, and Head of R&D. "We have carefully built the GRANITE platform and studied it in a translationally rich clinical program, demonstrating the sequence of desired biological events playing out in advanced cancer patients. Specifically, we showed de novo induction of neoantigen-specific T cells, trafficking of those same T cells to tumors, conversion of cold to hot tumor microenvironments, and key anti-tumor effects such as pseudo-progression, molecular responses, and suggestions of extended overall survival in molecular responders. In a tough tumor type such as metastatic colorectal cancer, these data are sufficiently striking to merit publication in Nature Medicine. We are proud of this accomplishment."

GRANITE is now being evaluated in two randomized studies in earlier-stage disease; 1) GRANITE-CRC-1L (NCT05141721), a Phase 2/3 trial in newly diagnosed metastatic, microsatellite-stable colorectal cancer (MSS-CRC) that has registrational intent. The first patient was treated in this study in July 2022, and initial results from this study are expected in the second half of 2023. 2) GRANITE-ADJUVANT (NCT05456165), a phase 2 study in patients with high-risk stage II/III colon cancer who are ctDNA+ after definitive surgery.

About GRANITE
Gritstone’s neoantigen-based immunotherapies are engineered to elicit a significant T cell response (particularly CD8+ cytotoxic T cells) against mutation-derived tumor-specific neoantigens (TSNA), that Gritstone identifies using its proprietary artificial intelligence platform, EDGE. GRANITE is an individualized neoantigen-based immunotherapy and uses a priming adenoviral vector (GRT-C901) and self-amplifying mRNA vector (GRT-R902) to deliver personalized immunotherapy containing the relevant neoantigens. GRANITE was granted Fast Track designation by the U.S. Food and Drug Administration for the treatment of MSS-CRC.