On August 8, 2023 Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX), (Nasdaq: CRNX) reported financial results for the second quarter ended June 30, 2023 (Press release, Crinetics Pharmaceuticals, AUG 8, 2023, View Source [SID1234633963]).

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"The PATHFNDR program for acromegaly continues to progress as expected. Topline results from our Phase 3 PATHFNDR-1 study are expected in September and should provide insight into paltusotine’s potential as an alternative to standard-of-care somatostatin receptor ligand depot injections. Enrollment in our Phase 3 PATHFNDR-2 study is also now complete and we anticipate topline results in the first quarter of 2024," said Scott Struthers, Ph.D., founder and chief executive officer of Crinetics. "Unfortunately, we also suffered a setback with our CRN04777 program and made the difficult decision to wind down its development. We know that infants and children living with congenital hyperinsulinism are in desperate need of better treatment options and our hearts go out to them and their families. However, our recently evolved understanding of the nonclinical profile of CRN04777 suggests that it no longer meets the high standards to which we hold all drug candidates in our pipeline."

SECOND QUARTER 2023 AND RECENT HIGHLIGHTS:
Topline data from paltusotine’s Phase 3 PATHFNDR-1 study expected in September 2023. PATHFNDR-1 is a placebo-controlled Phase 3 clinical study of oral paltusotine in participants with acromegaly switching from standard-of-care peptide depots. The study enrolled 58 participants with acromegaly whose average IGF-1 levels during screening were within the normal range (IGF-1 ≤ 1.0x upper limit of normal) on octreotide or lanreotide depot monotherapy. The primary endpoint of the study is the proportion of participants whose average IGF-1 levels at weeks 34 and 36 are within the normal range after switching to paltusotine compared to placebo.
Completed enrollment in paltusotine’s Phase 3 PATHFNDR-2 study. PATHFNDR-2 is a placebo-controlled Phase 3 clinical study of oral paltusotine in participants with acromegaly who are treatment-naïve or not currently receiving medical therapy. The study completed enrollment of 112 participants with acromegaly who were either treatment-naïve or untreated for at least four months (Stratum 1: n=82), or who washed out of prior octreotide or lanreotide monotherapy (Stratum 2: n=30). Topline data from the study is expected in the first quarter of 2024.
Paltusotine NDA submission anticipated in 2024. Pending successful data from the PATHFNDR program, Crinetics plans to submit a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) seeking regulatory approval for the use of paltusotine in acromegaly with both treatment and maintenance of treatment indications.
Clinical and preclinical data presented at the ENDO 2023 Annual Conference. A podium presentation featured results from the ACROBAT Advance open-label extension study of paltusotine in acromegaly. In addition, pre-clinical studies of the company’s thyroid-stimulating hormone (TSH) receptor antagonist for the treatment of thyroid eye disease (orbitopathy) associated with Graves’ disease and of the parathyroid hormone receptor type 1 (PTH1R) antagonist being developed for the treatment of primary hyperparathyroidism (PHPT) were presented as poster presentations. In addition, Scott Struthers, Ph.D., Crinetics’ founder and CEO was awarded the John D. Baxter Prize to recognize extraordinary achievement in endocrinology entrepreneurship at ENDO 2023 and gave an award lecture on the history of discovering nonpeptide oral drugs acting at peptide hormone receptors.
Phase 2 open-label study of paltusotine in carcinoid syndrome ongoing. The Phase 2 open-label study of paltusotine in carcinoid syndrome associated with neuroendocrine tumors is continuing to enroll participants, and preliminary data is anticipated in the fourth quarter of 2023.
CRN04894 studies in Cushing’s disease and congenital adrenal hyperplasia are ongoing. Based on successful Phase 1 studies demonstrating pharmacologic proof-of-concept, Crinetics is conducting clinical studies of CRN04894 in Cushing’s disease and congenital adrenal hyperplasia. Data from both studies are expected in 2024.
CRN04777 update. While developing our response to the clinical hold issued by the FDA, results from additional nonclinical studies became available. These studies uncovered findings at exposure levels that eroded anticipated therapeutic margins for CRN04777. These other findings are not related to those originally cited by the FDA for the clinical hold and, importantly, are not present in nonclinical studies that have been conducted with other Crinetics product candidates under development. We believe them to be specific to CRN04777 and not associated with its somatostatin receptor type 5 (SST5) mechanism of action. In light of these findings, the company has decided to suspend further significant investment into the molecule at this time.
SECOND QUARTER 2023 FINANCIAL RESULTS
Research and development expenses were $40.6 million for the three months ended June 30, 2023, compared to $33.0 million for the same period in 2022. The increase was primarily attributable to an increase in personnel costs of $6.9 million, increased consulting and outside services of $1.6 million, increased other expenditures of $0.7 million, partially offset by decreased net spending on manufacturing and development activities of $1.6 million associated with our clinical and nonclinical programs.
General and administrative expenses were $13.3 million for the three months ended June 30, 2023, compared to $10.5 million for the same period in 2022. The increase was primarily attributable to an increase in personnel costs of $2.7 million.
Net loss for the three months ended June 30, 2023, was $51.0 million, compared to a net loss of $42.4 million for the same period in 2022.
Revenues were $1.0 million for the three months ended June 30, 2023, compared to $0.4 million for the same period in 2022. Revenues in both periods were primarily derived from the paltusotine licensing arrangement with Sanwa Kagaku Kenkyusho Co., Ltd.
Unrestricted cash, cash equivalents, and investments totaled $264.5 million as of June 30, 2023, compared to $334.4 million as of December 31, 2022.
The company had 54,686,550 common shares outstanding as of August 4, 2023.
KEY OPINION LEADER (KOL) WEBINAR ON ACROMEGALY CURRENT TREATMENT LANDSCAPE AND UNMET NEED
Crinetics is hosting a KOL webinar today, August 8, 2023 at 12:00 pm ET. The webinar will feature key opinion leaders Beverly MK Biller, M.D. and Karen JP Liebert, R.N., B.S.N, both of Massachusetts General Hospital, who will discuss the current landscape and unmet medical need in acromegaly, as well as the treatment burden associated with standard-of-care injectable somatostatin receptor ligands (SRLs). In addition, the Crinetics management team will discuss its pipeline of internally discovered oral small molecule drug candidates, with a focus on the Phase 3 PATHFNDR-1 study of paltusotine.

A live question and answer session will follow the formal presentations. To register for the event, please click here. If you would like to ask a question during the live Q&A, please submit your request to [email protected]. A replay of the event will be available by clicking here.

On August 8, 2023 Corvus Pharmaceuticals, Inc. (Corvus or the Company) (Nasdaq: CRVS), a clinical-stage biopharmaceutical company, reported a business update and provided financial results for the second quarter ended June 30, 2023 (Press release, Corvus Pharmaceuticals, AUG 8, 2023, View Source [SID1234633962]).

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"During the second quarter, we continued to strengthen the scientific and clinical foundation for the potential use of soquelitinib for a variety of cancers and have several important near-term milestones for our clinical programs," said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. "We believe that soquelitinib, our selective ITK inhibitor, may offer a new approach to cancer immunotherapy based on its unique mechanism of action, which is to increase infiltration of cytotoxic T cells into tumors, increase the cytolytic capacity of T cells and reduce T cell exhaustion. This mechanism is distinct and independent from current immuno-oncology therapies based on checkpoint inhibition. We remain on track to meet with the FDA this quarter to discuss a potential registrational Phase 3 clinical trial with soquelitinib in relapsed T cell lymphomas (TCL). We also are planning to initiate clinical studies with soquelitinib in solid tumors. Lastly, enrollment is ongoing in clinical trials evaluating our partner led programs, ciforadenant and mupadolimab, with the potential for initial ciforadenant data from the Phase 1b/2 trial in front line therapy for patients with metastatic renal cell cancer to be released by year end."

Business Update and Strategy

Prioritized Program: Soquelitinib (formerly CPI-818, Corvus’ selective ITK inhibitor)

Soquelitinib for T Cell Lymphoma

Corvus continues to enroll patients with relapsed TCL in a Phase 1/1b clinical trial evaluating single agent therapy with soquelitinib, including utilizing its recently incorporated biomarker based on absolute lymphocyte count (ALC). The latest data from the trial was reported at the International Conference on Malignant Lymphoma, which took place June 13-17, 2023 in Lugano, Switzerland. As of the May 18, 2023 cut-off date, a total of 30 patients were enrolled at the optimum 200 mg two-times a day dose, including 20 evaluable for tumor response. There were 3 complete responses (CR) and 3 partial responses (PR) with one of these PRs demonstrating continued regression of the tumor. One of the patients with a CR and two with PRs remained on therapy. A total of ten patients remained on therapy, including six who have not had their initial tumor response evaluation. For patients with ALC above 900 per cubic milliliter of blood, objective responses (CR plus PR) were seen in 6 of 14 patients with disease control (CR, PR and stable disease) in 12 of 14 patients. No objective responses were seen in six patients (0 for 6) with ALC below 900.
Based on the current enrollment rate of the Phase 1/1b clinical trial, Corvus believes that the number of patients treated in this clinical trial would provide adequate safety and preliminary efficacy data to inform the design of a potential registrational Phase 3 randomized clinical trial. As recommended by the FDA, Corvus plans to meet with the FDA to discuss such a clinical trial; it is anticipated that this meeting will take place during the third quarter of this year.
Soquelitinib Preclinical Data in Hematologic and Solid Tumors

On July 6, 2023, Corvus announced the publication of preclinical data on soquelitinib as a preprint at bioRxiv, which highlighted the selective inhibition of ITK to potentially enhance anti-tumor immune response to hematologic and solid tumors and provide a novel approach to cancer immunotherapy. Important findings from the preclinical studies include the demonstration of soquelitinib’s ability to induce skewing and enrichment of T-helper type 1 (Th1) cells and increase infiltration of cancer killing T cells into tumors with greater potency and less resistance due to exhaustion. Data also showed that soquelitinib monotherapy led to in vivo anti-tumor activity in several mouse tumor models, including colon, renal, melanoma, B cell and T cell tumors.
Partner Led Programs: Ciforadenant (adenosine 2a receptor inhibitor) and Mupadolimab (anti-CD73)

The Kidney Cancer Research Consortium (KCRC) is enrolling a Phase 1b/2 clinical trial evaluating ciforadenant as a potential first line therapy for metastatic renal cell cancer (RCC) in combination with ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1). The Phase 1b portion of this trial has been completed and patients are now being enrolled in the Phase 2 portion. The clinical trial is expected to enroll up to 60 patients and initial data is anticipated before the end of 2023.

Support for the mechanism of action and anti-tumor activity of ciforadenant was recently presented at the Japanese Cancer Association and American Association for Cancer Research (AACR) (Free AACR Whitepaper) (JCA-AACR) Precision Cancer Medicine International Conference, which took place June 28-30, 2023 in Kyoto, Japan. The presentation highlighted preclinical data suggesting a synergy between ciforadenant and immune checkpoint blockade (ICB), leading to a proinflammatory response.
Angel Pharmaceuticals, Corvus’ partner in China, is enrolling patients in a Phase 1/1b clinical trial of mupadolimab in patients with non-small cell lung cancer (NSCLC) and head and neck squamous cell cancers. In this clinical trial, patients will receive mupadolimab monotherapy or in combination with pembrolizumab.
Financial Results
As of June 30, 2023, Corvus had cash, cash equivalents and marketable securities of $37.0 million as compared to $42.3 million as of December 31, 2022. During the quarter ending June 30, 2023, the Company sold 2,329,851 shares of its common stock through its at-the-market (ATM) program, generating net proceeds to the Company of $7.5 million. Corvus expects full year 2023 net cash used in operating activities to be between approximately $20 million and $22 million, resulting in a projected cash balance of between $28 million and $30 million as of December 31, 2023. Based on its current plans, Corvus expects its cash to fund operations into the second half of 2024.

Research and development expenses for the three months ended June 30, 2023 totaled $4.0 million compared to $4.9 million for the same period in 2022. The decrease of $0.9 million was primarily due to lower clinical trial and manufacturing costs associated with the development of mupadolimab.

The net loss for the three months ended June 30, 2023 was $6.5 million compared to a net loss of $8.4 million for the same period in 2022. Total stock compensation expense for the three months ended June 30, 2023 was $0.5 million compared to $0.7 million for the same period in 2022 and the non-cash loss from Corvus’ equity method investment in Angel Pharmaceuticals was $1.3 million for the three months ended June 30, 2023 compared to $1.6 million in the same period in 2022.

Conference Call Details
Corvus will host a conference call and webcast today, Tuesday, August 8, 2023, at 4:30 p.m. ET (1:30 p.m. PT), during which time management will provide a business update and discuss the second quarter 2023 financial results. The conference call can be accessed by dialing 1-855-327-6837 (toll-free domestic) or 1-631-891-4304 (international) or by clicking on this link for instant telephone access to the event. The live webcast may be accessed via the investor relations section of the Corvus website. A replay of the webcast will be available on Corvus’ website for 90 days.

On August 8, 2023 Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, reported financial results for the second quarter ended June 30, 2023 (Press release, Cogent Biosciences, AUG 8, 2023, View Source [SID1234633961]).

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"Cogent continues to deliver on our mission to bring best-in-class therapies to patients with genetically defined diseases," said Andrew Robbins, the Company’s President and Chief Executive Officer. "During the second quarter we presented positive data from the lead-in portion of our ongoing Phase 3 PEAK study reinforcing our belief that the combination of bezuclastinib and sunitinib has the potential to become a new treatment option for second-line GIST patients. With great support from new and existing investors, we completed a public equity offering that has put us in a very strong financial position, extending our cash runway into 2026. As we turn to the second half of 2023, we look forward to presenting initial results from the SUMMIT trial with bezuclastinib in patients with non-advanced systemic mastocytosis as well as presenting updated APEX data with bezuclastinib in patients with advanced systemic mastocytosis. Finally, we are excited to announce the selection of our FGFR2 clinical candidate, which we believe has a best-in-class potency and selectivity profile. We plan to present additional preclinical data later this year and are on track to initiate clinical trials in 2024."

Recent Business Highlights

Presented positive lead-in data from the ongoing Phase 3 PEAK trial evaluating bezuclastinib in combination with sunitinib in patients with Gastrointestinal Stromal Tumors (GIST) at the 2023 ASCO (Free ASCO Whitepaper) annual meeting.
As of the cutoff date of March 29, 2023, data demonstrated a 55% Disease Control Rate (DCR) in heavily pre-treated GIST patients, including 100% DCR and 17% overall response rate (ORR) in efficacy evaluable 2nd-line GIST patients.
The combination of bezuclastinib and sunitinib was generally well-tolerated with an encouraging safety profile.
Selected a potent, selective, reversible FGFR2 kinase inhibitor as the first internally developed clinical candidate from the Cogent Research Team.
In vivo characterization of the candidate shows a novel, selective, reversible FGFR2 inhibitor that has potency against molecular brake and gatekeeper mutations, with potential advantages over current covalent approaches.
Presented preclinical data describing a novel EGFR-sparing, brain-penetrant ErbB2 inhibitor with potency across key oncogenic ErbB2 mutations at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) annual meeting.
Closed an underwritten public offering of 14,375,000 shares of common stock at a public offering price of $12.00 per share, including an additional 1,875,000 shares of common stock related to the underwriters’ option, which was exercised in full. Cogent received estimated net proceeds of approximately $161.8 million, after deducting underwriting discounts and commissions and estimated offering expenses.
Upcoming Milestones

Present initial clinical data from SUMMIT, a randomized, double-blind, placebo-controlled, global, multicenter, Phase 2 clinical trial of bezuclastinib in patients with non-advanced systemic mastocytosis (NonAdvSM) in the second half of 2023. Data will include safety/tolerability and measures of clinical activity.
Present updated clinical data from approximately 30 patients in Part 1 of APEX, a global, multicenter Phase 2 clinical trial of bezuclastinib in patients with advanced systemic mastocytosis (AdvSM) at a scientific meeting in the second half of 2023.
Upcoming Investor Conference

Cogent will participate in the Morgan Stanley 21st Annual Global Healthcare Conference on Wednesday, September 13, 2023 at 8:10 a.m. ET.
A live webcast of the event can be accessed on the Investors & Media page of Cogent’s website at investors.cogentbio.com/events. A replay will be available approximately two hours after completion of the event and will be archived for up to 30 days.
Second Quarter 2023 Financial Results

Cash Position: As of June 30, 2023, cash, cash equivalents and marketable securities were $350.9 million, as compared to $220.3 million as of March 31, 2023. The company expects its existing cash, cash equivalents and marketable securities will be sufficient to fund its operating expenses and capital expenditure requirements into 2026.

R&D Expenses: Research and development expenses were $38.9 million for the second quarter of 2023 as compared to $29.5 million for the second quarter of 2022. The increase was primarily due to costs associated with the on-going APEX, SUMMIT and PEAK clinical trials and costs related to development of the research pipeline. R&D expenses include non-cash stock compensation expense of $3.6 million for the second quarter of 2023 compared to $2.1 million for the second quarter of 2022.

G&A Expenses: General and administrative expenses were $8.2 million for the second quarter of 2023 as compared to $6.4 million for the second quarter of 2022. The increase was primarily due to the growth of the organization. G&A expenses include non-cash stock compensation expense of $3.6 million for the second quarter of 2023 compared to $2.4 million for the second quarter of 2022.

Net Loss: Net loss was $44.1 million for the second quarter of 2023 as compared to a net loss of $34.9 million for the same period of 2022.

On August 8, 2023 Celldex Therapeutics, Inc. (NASDAQ:CLDX) reported financial results for the second quarter ended June 30, 2023 and provided a corporate update (Press release, Celldex Therapeutics, AUG 8, 2023, View Source [SID1234633960]).

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"Last month, we announced that enrollment in our Phase 2 chronic spontaneous urticaria trial was completed well ahead of schedule, exceeding projections by nearly 25%, driven by strong interest in barzolvolimab," said Anthony Marucci, Co-founder, President and Chief Executive Officer of Celldex Therapeutics. "Enrollment also continues to progress as planned in our Phase 2 study in chronic inducible urticaria. We are extremely pleased with the progress we have made across both of these studies and look forward to presenting topline data from the CSU study by the end of the year."

"The rest of our pipeline also continues to advance and we were excited to recently initiate a Phase 2 study in eosinophilic esophagitis and are planning for the initiation of a Phase 2 study in prurigo nodularis in early 2024. In June, barzolvolimab was highlighted in multiple presentations at EAACI that continue to position the program as a potential best-in-class addition to a historically limited treatment landscape for patients and their physicians. We look forward to building on this momentum in the second half of the year," concluded Marucci.

Recent Program Highlights

Barzolvolimab – KIT Inhibitor Program

Barzolvolimab is a humanized monoclonal antibody developed by Celldex that binds the KIT receptor with high specificity and potently inhibits its activity. The KIT receptor tyrosine kinase is expressed in a variety of cells, including mast cells, which mediate inflammatory responses such as hypersensitivity and allergic reactions. KIT signaling controls the differentiation, tissue recruitment, survival and activity of mast cells.

In June and July 2022, Celldex announced that the first patients had been dosed in the Phase 2 clinical studies of barzolvolimab for the treatment of Chronic Spontaneous Urticaria (CSU) and the two most common forms of chronic inducible urticaria (CIndU) – cold urticaria (ColdU) and symptomatic dermographism (SD). These randomized, double-blind, placebo-controlled, parallel group Phase 2 studies are evaluating the efficacy and safety profile of multiple dose regimens of barzolvolimab in patients who remain symptomatic despite antihistamine therapy, to determine the optimal dosing strategies. In July 2023, Celldex announced that enrollment to the CSU study had been completed. Given strong interest in barzolvolimab, enrollment projections were exceeded by ~25% and 208 patients were enrolled in the study. Topline data is anticipated by the end of 2023.

Updated data from the Phase 1b multiple dose study in patients with antihistamine refractory CSU and new data from the Phase 1b single-dose cholinergic cohort included in the CIndU trial were presented at the European Academy of Allergy and Clinical Immunology (EAACI) Annual Congress on June 10, 2023 by Dr. Marcus Maurer, Professor of Dermatology and Allergy at Charité – Universitätsmedizin in Berlin (CSU data) and Dr. Eva Grekowitz, Clinical Investigator, Department of Dermatology, Venerology and Allergy at Charité – Universitätsmedizin in Berlin (cholinergic data).
CSU EAACI 2023 Data Summary:

At EAACI 2023, data were presented on the complete 24 week experience for all patients. 45 patients with moderate to severe CSU refractory to antihistamines were enrolled and treated [35 barzolvolimab (n=9 in 0.5 mg/kg; n=8 in 1.5 mg/kg; n=9 in 3.0 mg/kg; n=9 in 4.5 mg/kg) and 10 placebo]. Treatment data for the 0.5 mg/kg and placebo group are not included below because as expected, most patients from these groups had significant symptoms ahead of week 24 and discontinued follow up.

Multiple doses of barzolvolimab resulted in rapid dose-dependent decreases in itch and hives with durable and prolonged symptom control in patients with moderate to severe CSU refractory to antihistamines, including patients with prior omalizumab treatment.

Mean reduction from baseline in urticaria activity (UAS7) at week 24 was 80% in the 1.5 mg/kg dose group (n=7), 70% in the 3.0 mg/kg dose group (n=6) and 77% in the 4.5 mg/kg dose group (n=7).

Complete response (UAS7=0) at week 24 was 57% in the 1.5 mg/kg dose group, 67% in the 3.0 mg/kg dose group and 43% in the 4.5 mg/kg dose group. Well-controlled disease (UCT≥ 12) at week 24 was 75% in the 1.5 mg/kg dose group, 67% in the 3.0 mg/kg dose group and 67% in the 4.5 mg/kg dose group. During post-treatment follow up, 71% (10 of 14) of patients who had been treated with doses greater than or equal to 1.5 mg/kg and had a complete response (UAS7=0) at week 12, remained urticaria free at week 24.

Profound and durable improvement in angioedema symptoms as measured through the angioedema activity score over 7 days (AAS7) was achieved across all dose levels evaluated with sustained activity observed with the 1.5 mg/kg and greater dose levels. 31 patients on study (n=26 barzolvolimab; 5=placebo) reported angioedema activity at baseline when enrolling in the study. 86% of the barzolvolimab treated patients at 1.5 mg/kg or greater were angioedema free at week 12 and 83% were angioedema free at week 24.

Barzolvolimab was well tolerated with a favorable safety profile; effects of multiple dose administration were consistent with observations in single dose studies.
Cholinergic (CholU) EAACI 2023 Data Summary:

At EAACI 2023, 12 week treatment and safety data were presented from the cohort of patients with antihistamine refractory cholinergic urticaria (n=9) included in the open-label, Phase 1 trial of chronic inducible urticaria. Patients received a single intravenous 3.0 mg/kg barzolvolimab dose with a 12-week follow-up.

56% (5/9) patients achieved a complete response (negative test) with PCE (pulse-controlled ergometry) provocation testing with just one dose of barzolvolimab and most responses remained durable through to week 12. PCE testing included controlled exercise on a stationary bicycle with monitoring for development of itch and wheals.

63% (5/8) patients reported well controlled disease (UCT ≥12) at week 8 and 50% (4/8) at week 12, respectively. 100% (6/6) patients who reported on quality of life (QoL) measurements at week 8 had clinically significant improvements in QoL. These improvements in QoL were sustained through week 12 for the majority (5/7, 71%) of patients.

The kinetics of tryptase and mast cell reduction mirrored clinical activity.

Barzolvolimab was generally well tolerated in patients with CholU, with a similar safety profile to what was reported previously in the cold contact and symptomatic dermographism cohorts in this study.
Celldex closed enrollment at 24 patients in the barzolvolimab Phase 1b multi-center, randomized, double-blind, placebo-controlled study in patients with prurigo nodularis (PN), a chronic skin disease characterized by the development of hard, intensely itchy (pruritic) nodules on the skin. The Company plans to present data from the study, including 24 weeks of follow-up, in the fourth quarter at a medical meeting and is planning for the initiation of a Phase 2 subcutaneous study in PN in early 2024.

In June, Celldex initiated a Phase 2 study of eosinophilic esophagitis (EoE) and the first patient was dosed in July. EoE, the most common type of eosinophilic gastrointestinal disease, is a chronic inflammatory disease of the esophagus characterized by the infiltration of eosinophils. The randomized, double-blind, placebo-controlled, parallel group Phase 2 study is evaluating the efficacy and safety profile of subcutaneous barzolvolimab in patients with active EoE. Approximately 60 patients will be enrolled. The primary endpoint of the study is reducing esophageal intraepithelial infiltration of mast cells as assessed by peak esophageal intraepithelial mast cell count. Secondary endpoints include the reduction of symptoms of dysphagia and esophageal intraepithelial infiltration of eosinophils and safety. When all clinical trial sites are open, the study will include approximately 60 clinical trial centers across 8 countries, including the United States.
Bispecific Antibody Platform

CDX-585 – Bispecific ILT4 & PD-1

CDX-585 combines highly active PD-1 blockade with anti-ILT4 blockade to overcome immunosuppressive signals in T cells and myeloid cells. ILT4 is emerging as an important immune checkpoint on myeloid cells.

In May 2023, Celldex announced that the first patient had been dosed in the Phase 1 study of CDX-585. This open-label, multi-center, intravenous study of CDX-585 is being evaluated in patients with advanced or metastatic solid tumors that have progressed during or after standard of care therapy. The dose-escalation phase of the study (n=~30 patients) is designed to determine a maximum tolerated dose (MTD) and to select CDX-585 dose(s) for future evaluation in tumor specific expansion cohorts.
Second Quarter 2023 Financial Highlights and 2023 Guidance

Cash Position: Cash, cash equivalents and marketable securities as of June 30, 2023 were $252.7 million compared to $278.4 million as of March 31, 2023. The decrease was primarily driven by second quarter cash used in operating activities of $27.2 million, partially offset by net sales and maturities of marketable securities of $1.6 million for the three months ended June 30, 2023. At June 30, 2023, Celldex had 47.3 million shares outstanding.

Revenues: Total revenue was $0.3 million in the second quarter of 2023 and $1.2 million for the six months ended June 30, 2023, compared to $0.2 million and $0.3 million for the comparable periods in 2022. The increase in revenue was primarily due to an increase in services performed under our manufacturing and research and development agreements with Rockefeller University.

R&D Expenses: Research and development (R&D) expenses were $26.3 million in the second quarter of 2023 and $53.0 million for the six months ended June 30, 2023, compared to $20.7 million and $37.8 million for the comparable periods in 2022. The increase in R&D expenses was primarily due to an increase in barzolvolimab clinical trial, barzolvolimab contract manufacturing and personnel expenses.

G&A Expenses: General and administrative (G&A) expenses were $7.2 million in the second quarter of 2023 and $13.9 million for the six months ended June 30, 2023, compared to $7.2 million and $14.1 million for the comparable periods in 2022. The decrease in G&A expenses for the six months ended June 30, 2023, as compared to the six months ended June 30, 2022, was primarily due to a decrease in legal expenses, partially offset by an increase in stock-based compensation expense.

Changes in Fair Value Remeasurement of Contingent Consideration: The gain on fair value remeasurement of contingent consideration was $6.3 million for the second quarter of 2022 and $6.9 million for the six months ended June 30, 2022, primarily due to the Company’s decision to deprioritize the CDX-1140 program in the second quarter of 2022.

Net Loss: Net loss was $30.5 million, or ($0.65) per share, for the second quarter of 2023, and $59.9 million, or ($1.27) per share, for the six months ended June 30, 2023, compared to a net loss of $36.0 million, or ($0.77) per share, for the second quarter of 2022, and $59.1 million, or ($1.26) per share, for the six months ended June 30, 2022.

Financial Guidance: Celldex believes that the cash, cash equivalents and marketable securities at June 30, 2023 are sufficient to meet estimated working capital requirements and fund planned operations through 2025, which include our ongoing and planned Phase 2 studies in CSU, CIndU, EoE and PN.

On August 8, 2023 Caribou Biosciences, Inc. (Nasdaq: CRBU), a leading clinical-stage CRISPR genome-editing biopharmaceutical company, reported financial results for the second quarter of 2023 and reviewed recent business updates (Press release, Caribou Biosciences, AUG 8, 2023, View Source [SID1234633959]).

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"In 2023, we have advanced our programs to build value across the pipeline and position Caribou for continued momentum ahead," said Rachel Haurwitz, PhD, Caribou’s president and chief executive officer. "For our lead program, we are excited by the positive CB-010 dose escalation data demonstrating response rates that rival those from the approved autologous CAR-T cell therapies. As we develop CB-010 for the larger second-line LCBL patient population, we continue to enroll patients in dose expansion and anticipate reporting initial dose expansion data in the first half of 2024. We also look forward to meeting with the FDA later this year to discuss a potential pivotal clinical trial in second-line LBCL patients. Additionally, we continue to enroll patients in our CaMMouflage trial for CB-011 and plan for an IND submission for CB-012 in the second half of this year."

Accomplishments and highlights

Pipeline and technology
•CB-010: Caribou reported [View Source long-term follow-up data from all 16 patients treated in dose escalation of the ongoing ANTLER Phase 1 clinical trial of CB-010, an allogeneic anti-CD19 CAR-T cell therapy. In ANTLER dose escalation, three dose levels of CB-010 were evaluated (40×106, 80×106, and 120×106 CAR-T cells) in patients with multiple subtypes of aggressive relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL). As of the June 20, 2023 data cutoff date, results demonstrated:
◦CB-010 was generally well tolerated with adverse events consistent with autologous and allogeneic anti-CD19 CAR-T cell therapies.
◦94% overall response rate (ORR; 15 of 16 patients) was observed following a single dose of CB-010.
◦69% of patients (11 of 16) achieved a complete response (CR).

◦44% of patients (7 of 16) had a CR at ≥6 months; 24 months is the longest CR maintained to date.
◦For the subset of patients with large B cell lymphoma (LBCL) (N=10):
▪A 90% ORR (9 of 10) was observed.
▪70% (7 of 10) achieved a CR.
▪50% (5 of 10) had a CR at ≥6 months; 18 months is the longest CR maintained to date.
◦Based on these positive data, Caribou is enrolling second-line patients with LBCL in the ongoing dose expansion portion of the ANTLER clinical trial. In expansion, the mid dose and the high dose from escalation (80×106 and 120×106 CAR-T cells) are being evaluated in approximately 30 second-line patients (approximately 15 patients per dose level) to determine the recommended Phase 2 dose (RP2D). Once the RP2D is determined, Caribou may enroll additional patients in ANTLER.
•CB-011: Caribou is enrolling patients at dose level 1 (50×106 CAR-T cells) in the dose escalation portion of the ongoing CaMMouflage Phase 1 trial of CB-011, an allogeneic anti-BCMA CAR-T cell therapy, for relapsed or refractory multiple myeloma (r/r MM).
•CB-012: Caribou is advancing IND-enabling activities for CB-012, an allogeneic anti-CLL-1 CAR-T cell therapy, for relapsed or refractory acute myeloid leukemia (r/r AML).

Anticipated milestones
•CB-010: Caribou plans to meet with the FDA to discuss a potential pivotal clinical trial in second-line LBCL patients and plans to share FDA feedback by YE 2023. The Company also plans to report initial dose expansion data in second-line LBCL patients from the ongoing ANTLER trial in H1 2024.
•CB-011: Caribou plans to provide updates on dose escalation as the CaMMouflage Phase 1 clinical trial in r/r MM advances.
•CB-012: Caribou plans to submit an IND application for r/r AML in H2 2023.

Corporate updates
•$25.0 million Pfizer investment: On June 30, 2023, Pfizer invested [View Source $25.0 million in Caribou common shares. In conjunction with the investment, Sriram Krishnaswami, PhD, joined Caribou’s scientific advisory board [View Source Caribou will use the proceeds from this investment to advance CB-011. Caribou maintains full ownership and control of CB-011 and its other allogeneic CAR-T and CAR-NK cell therapies.
•Completed successful $134.6 million follow-on financing: In the third quarter of 2023, Caribou completed an underwritten public offering of 22,115,384 shares of its common stock, which included the full exercise of the underwriters’ option to purchase additional shares. The approximate net proceeds to Caribou were $134.6 million.

Second quarter 2023 financial results

Cash, cash equivalents, and marketable securities: Caribou had $292.5 million in cash, cash equivalents, and marketable securities as of June 30, 2023, which included the $25.0 million proceeds from the Pfizer investment, compared to $317.0 million as of December 31, 2022. This amount does not include the approximately $134.6 million in net proceeds from the Company’s underwritten public offering completed in the third quarter of 2023. Caribou expects its cash, cash equivalents, marketable securities, and net proceeds from the recent public offering will be sufficient to fund its current operating plan into Q4 2025.

Licensing and collaboration revenue: Revenue from Caribou’s licensing and collaboration agreements was $3.8 million for the three months ended June 30, 2023, compared to $4.2 million for the same period 2022. The decrease was primarily due to a reduction in revenue recognized under the AbbVie Collaboration and License Agreement, partially offset by a revenue increase related to a veterinary therapeutics licensing agreement.
R&D expenses: Research and development expenses were $26.5 million for the three months ended June 30, 2023, compared to $22.6 million for the same period in 2022. The increase was primarily due to personnel-related expenses, including stock-based compensation; costs to advance pipeline programs, including the ANTLER and CaMMouflage Phase 1 trials; and facilities and other allocated expenses.

G&A expenses: General and administrative expenses were $10.1 million for the three months ended June 30, 2023, compared to $10.0 million for the same period in 2022. The increase was primarily due to facilities and other allocated expenses; patent prosecution and maintenance costs; and personnel-related expenses, including stock-based compensation, due to headcount increases. The increase was partially offset by lower insurance and legal expenses.
Net loss: Caribou reported a net loss of $29.5 million for the three months ended June 30, 2023, compared to $26.7 million for the same period in 2022.

About CB-010
CB-010 is the lead product candidate from Caribou’s allogeneic CAR-T cell therapy platform and is being evaluated in patients with relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL). In the ongoing ANTLER Phase 1 trial, Caribou is enrolling second-line patients with large B cell lymphoma (LBCL) comprising four different subtypes of aggressive r/r B-NHL (DLBCL NOS, PMBCL, HGBL, and tFL). CB-010 is an allogeneic anti-CD19 CAR-T cell therapy engineered using Cas9 CRISPR hybrid RNA-DNA (chRDNA) technology. To Caribou’s knowledge, CB-010 is the first allogeneic CAR-T cell therapy in the clinic with a PD-1 knockout, a genome-editing strategy designed to improve antitumor activity by limiting premature CAR-T cell exhaustion. To Caribou’s knowledge, CB-010 is also the first anti-CD19 allogeneic CAR-T cell therapy to be evaluated in the second-line LBCL setting and it has been granted Regenerative Medicine Advanced Therapy (RMAT), Fast Track, and Orphan Drug designations by the FDA. Additional information on the ANTLER trial (NCT04637763) can be found at clinicaltrials.gov.

About CB-011
CB-011 is the second product candidate from Caribou’s allogeneic CAR-T cell therapy platform and is being evaluated in patients with relapsed or refractory multiple myeloma (r/r MM) in the CaMMouflage Phase 1 trial. CB-011 is an allogeneic anti-BCMA CAR-T cell therapy engineered using Cas12a chRDNA technology. To Caribou’s knowledge, CB-011 is the first allogeneic CAR-T cell therapy in the clinic that is engineered to improve antitumor activity through an immune cloaking strategy with a B2M knockout and insertion of a B2M–HLA-E fusion protein to blunt immune-mediated rejection. CB-011 has been granted Fast Track designation by the FDA. Additional information on the CaMMouflage trial (NCT05722418) can be found at clinicaltrials.gov.

About CB-012
CB-012 is the third product candidate from Caribou’s allogeneic CAR-T cell therapy platform and is being evaluated in investigational new drug (IND)-enabling studies. To Caribou’s knowledge, CB-012 is the first allogeneic CAR-T cell therapy with both checkpoint disruption, through a PD-1 knockout, and immune cloaking, through a B2M knockout and B2M–HLA-E fusion protein insertion; both armoring strategies are designed to improve antitumor activity. CB-012 is engineered with five genome edits, enabled by Caribou’s patented next-generation CRISPR technology platform, which uses Cas12a chRDNA genome editing to significantly improve the specificity of genome edits.