On August 5, 2024 ESSA Pharma Inc. ("ESSA", or the "Company") (NASDAQ: EPIX), a clinical-stage pharmaceutical company focused on developing novel therapies for the treatment of prostate cancer, reported a corporate update and provided financial results for the fiscal third quarter ended June 30, 2024 (Press release, ESSA, AUG 5, 2024, View Source [SID1234645353]).

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"With continued focus on execution, we are progressing towards a stream of significant milestones throughout the next nine to twelve months, with the first being the presentation at ESMO (Free ESMO Whitepaper) of more mature durability data from the Phase 1 dose escalation study evaluating masofaniten combined with enzalutamide in patients with metastatic castration-resistant prostate cancer naïve to second-generation antiandrogens," said David Parkinson, MD, President and CEO of ESSA. "We are focused on the enrollment of the Phase 2 dose expansion study evaluating masofaniten in combination with enzalutamide, with 25 sites activated in the US, Canada and Australia and an additional 14 sites being activated in Europe. We look forward to reporting key data across these trials throughout the remainder of this year through 2025."

Third Quarter Fiscal 2024 and Recent Highlights

Masofaniten Combination Studies

Phase 1/2 study is still ongoing evaluating masofaniten in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer ("mCRPC") naïve to second-generation antiandrogens but may have been treated with chemotherapy in the metastatic castration-sensitive setting. The latest reported results, which were presented at the ASCO (Free ASCO Whitepaper)-GU symposium in January 2024, demonstrated that the combination regimen continues to be well tolerated at the dose levels tested in up to 25 cycles of dosing in some patients. Reductions in PSA were observed across evaluable patients for efficacy in all dosing cohorts (n=16). Across all dosing cohorts, 88% of patients achieved PSA50, 81% of patients achieved PSA90, 69% of patients achieved PSA90 in less than 90 days, and 63% of patients achieved PSA <0.2ng/mL. While the data for time to PSA progression were still maturing, the median time to PSA progression was reported as 16.6 months with a median follow up at that time of 11.1 months. ESSA plans to report updated data from the Phase 1 dose escalation study at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2024 congress.
Masofaniten continues to be evaluated in combination with enzalutamide compared to enzalutamide monotherapy in a Phase 2 dose randomized study in patients with mCRPC naïve to second-generation antiandrogens but who may have been treated with chemotherapy in the metastatic castration-sensitive setting. Enrollment in the Phase 2 portion of this Phase 1/2 study is expected to be completed during the first quarter of 2025. The study is currently enrolling at approximately 25 sites in the US, Canada, and Australia. Expansion to European clinical sites is in progress with an additional 14 clinical sites planned to be activated by the third quarter of 2024. ESSA is on track to report preliminary data from the Phase 2 dose expansion portion of the study in mid-2025.
Two additional masofaniten combination arms are continuing enrollment as part of the ongoing Phase 1 masofaniten study. One arm is evaluating masofaniten in combination with abiraterone acetate and prednisone in patients with either metastatic castration-sensitive prostate cancer or mCRPC, while the second arm is evaluating masofaniten in combination with apalutamide in patients with non-metastatic castration-resistant prostate cancer after 12 weeks of masofaniten single agent.
Two additional investigator-sponsored studies testing combinations of masofaniten with darolutamide or enzalutamide in different patient populations are currently enrolling: a) an Australian investigator-sponsored neoadjuvant study evaluating neoadjuvant use of the combination of masofaniten and darolutamide compared to darolutamide monotherapy in high-risk patients undergoing prostatectomy and b) an investigator-sponsored study which is testing masofaniten and enzalutamide in metastatic castration-sensitive prostate cancer patients.
Masofaniten Monotherapy Study

ESSA remains on track to complete the Phase 1b masofaniten monotherapy study evaluating masofaniten in patients with mCRPC resistant to second-generation antiandrogens. The initial results from the monotherapy study were reported at the 2023 ASCO (Free ASCO Whitepaper)-GU Symposium, and demonstrated that masofaniten monotherapy was well-tolerated, achieved clinically significant exposures, and showed preliminary signals of anti-tumor activity in a subset of patients. ESSA plans to present the complete Phase 1b monotherapy results in the second half of 2024 at a medical conference.
Summary Financial results
(Amounts expressed in U.S. dollars)

Net Loss. ESSA recorded a net loss of $7.2 million for the third quarter ended June 30, 2024, compared to $7.3 million for the third quarter ended June 30, 2023.
Research and Development ("R&D") expenditures. R&D expenditures for the third quarter ended June 30, 2024, were $5.5 million compared to $6.3 million for the third quarter ended June 30, 2023, and include non-cash costs related to share-based payments of $851,971 for the third quarter ended 2024 compared to $599,621 for the third quarter ended 2023. The decrease is largely attributable to reductions in preclinical work with the focus on ongoing clinical trials.
General and Administration ("G&A") expenditures. G&A expenditures for the third quarter ended June 30, 2024, were $3.2 million compared to $2.6 million for the third quarter ended June 30, 2023, and include non-cash costs related to share-based payments of $1,748,227 for the third quarter ended 2024 compared to $561,452 for the third quarter ended 2023. The net decrease (net of share-based payments) relates to the timing of corporate projects and lower insurance premiums for the current period.
Liquidity and Outstanding Share Capital

As of June 30, 2024, the Company had available cash reserves and short-term investments of $130.7 million. The Company’s cash position is expected to be sufficient to fund current and planned operations beyond 2025.
As of June 30, 2024, the Company had 44,368,959 common shares issued and outstanding.
In addition, as of June 30, 2024, there were 2,920,000 common shares issuable upon the exercise of prefunded warrants at an exercise price of $0.0001.

On August 5, 2024 Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, reported its financial results for the second quarter and six months ended June 30, 2024 (Press release, Castle Biosciences, AUG 5, 2024, View Source [SID1234645334]).

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"We achieved another quarter of exceptional performance, thanks to the hard work of our talented team and strength of our innovative test portfolio," said Derek Maetzold, president and chief executive officer of Castle Biosciences. "We were especially pleased with the substantial top-line growth as well as growth in test report volumes across our therapeutic areas."

"Regarding our DecisionDx-SCC test, we were also pleased to see the publication of our first study evaluating the use of DecisionDx-SCC to guide adjuvant radiation therapy (ART) recommendations in patients diagnosed with high-risk cutaneous squamous cell carcinoma (SCC). This study, which is the largest study to evaluate the effectiveness of ART in SCC, found that the DecisionDx-SCC test can identify patients who are considering ART under traditional clinicopathologic risk features and have a low likelihood of metastasis and a low likelihood of a receiving a clinical benefit from ART – thus enabling deferral of radiation therapy and avoidance of complications and associated impacts on the patient’s quality of life. This study was published in the American Society for Radiation Oncology’s flagship journal, International Journal of Radiation Oncology, Biology, Physics (also known as the Red Journal).

"Regarding our TissueCypher Barrett’s Esophagus test, the American Gastroenterological Association (AGA) recently recognized in its Clinical Practice Guideline that there is a high-risk subset of non-dysplastic Barrett’s esophagus patients who may benefit from early intervention with endoscopic eradication therapy (EET) and importantly, acknowledged that tissue-based biomarker testing, including the tissue systems pathology test (i.e., TissueCypher, also known as TSP-9) can help identify these patients.

"We believe we are well-positioned for near- and long-term success, supported by the potential for continued growth across our portfolio, as well as by our robust balance sheet and proven track record of strong execution. I am proud of what we have accomplished, and we will continue to work to operate with speed and agility to deliver value to patients, clinicians and stockholders alike."

Second Quarter Ended June 30, 2024, Financial and Operational Highlights
•Revenues were $87.0 million, a 74% increase compared to $50.1 million in the second quarter of 2023. Included in revenue for the period were revenue adjustments related to tests delivered in prior periods. These prior period revenue adjustments for the quarter were $0.4 million of net positive revenue adjustments, compared to $0.1 million of net negative revenue adjustments for the same period in 2023.
•Adjusted Revenues, which exclude the effects of revenue adjustments related to tests delivered in prior periods, were $86.6 million, a 72% increase compared to $50.2 million for the same period in 2023.
•Delivered 25,102 total test reports in the second quarter of 2024, an increase of 49% compared to 16,820 in the same period of 2023:
◦DecisionDx-Melanoma test reports delivered in the quarter were 9,585, compared to 8,597 in the second quarter of 2023, an increase of 11%.

◦DecisionDx-SCC test reports delivered in the quarter were 4,277, compared to 2,681 in the second quarter of 2023, an increase of 60%.
◦MyPath Melanoma test reports delivered in the quarter were 1,099, compared to 953 in the second quarter of 2023, an increase of 15%.
◦TissueCypher Barrett’s Esophagus test reports delivered in the quarter were 4,782, compared to 1,447 in the second quarter of 2023, an increase of 230%.
◦IDgenetix test reports delivered in the quarter were 4,903, compared to 2,681 in the second quarter of 2023, an increase of 83%.
◦DecisionDx-UM test reports delivered in the quarter were 456, compared to 461 in the second quarter of 2023, a decrease of 1%.
•Gross margin was 81%, and Adjusted Gross Margin was 83%, compared to 74% and 78%, respectively, for the same periods in 2023.
•Net cash provided by operations was $24.0 million, compared to $3.8 million net cash used in operations for the same period in 2023.
•Net income, which includes non-cash stock-based compensation expense of $13.2 million, was $8.9 million, compared to a net loss of $(18.8) million for the same period in 2023.
•Adjusted EBITDA was $21.5 million, compared to $(5.3) million for the same period in 2023.

Six Months Ended June 30, 2024, Financial and Operational Highlights
•Revenues were $160.0 million, a 74% increase compared to $92.2 million during the same period in 2023. Included in revenue for the period were revenue adjustments related to tests delivered in prior periods. These prior period revenue adjustments for the six months ended June 30, 2024, were $1.0 million of net positive revenue adjustments, compared to $1.7 million of net negative revenue adjustments for the same period in 2023.
•Adjusted Revenues, which exclude the effects of revenue adjustments related to tests delivered in prior periods, were $159.0 million, a 69% increase compared to $93.9 million for the same period in 2023.
•Delivered 45,990 total test reports in the six months ended June 30, 2024, an increase of 45% compared to 31,736 in the same period of 2023:
◦DecisionDx-Melanoma test reports delivered in the six months ended June 30, 2024, were 17,969, compared to 16,180 for the same period in 2023, an increase of 11%.
◦DecisionDx-SCC test reports delivered in the six months ended June 30, 2024, were 7,854, compared to 5,092 for the same period in 2023, an increase of 54%.
◦MyPath Melanoma test reports delivered in the six months ended June 30, 2024, were 2,097, compared to 1,933 for the same period in 2023, an increase of 8%.
◦TissueCypher Barrett’s Esophagus test reports delivered in the six months ended June 30, 2024, were 8,211, compared to 2,830 for the same period in 2023, an increase of 190%.
◦IDgenetix test reports delivered in the six months ended June 30, 2024, were 8,981, compared to 4,831 for the same period in 2023, an increase of 86%.
◦DecisionDx-UM test reports delivered in the six months ended June 30, 2024, were 878, compared to 870 for the same period in 2023, an increase of 1%.
•Gross margin for the six months ended June 30, 2024, was 79%, and Adjusted Gross Margin was 82%.
•Net cash provided by operations was $17.2 million, compared to $29.2 million net cash used in operations for the same period in 2023.
•Net income for the six months ended June 30, 2024, which includes non-cash stock-based compensation expense of $25.9 million, was $6.4 million, compared to a net loss of $(48.0) million for the same period in 2023.
•Adjusted EBITDA for the six months ended June 30, 2024, was $32.1 million, compared to $(20.4) million for the same period in 2023.
Cash, Cash Equivalents and Marketable Investment Securities
As of June 30, 2024, the Company’s cash, cash equivalents and marketable investment securities totaled $259.7 million.

2024 Outlook
Based upon revenue generated through June 30, 2024, the Company is increasing its guidance for anticipated total revenue in 2024 to between $275–300 million, compared to the previously provided guidance of between $255–265 million.
Second Quarter and Recent Accomplishments and Highlights
Dermatology
•DecisionDx-SCC: The Company announced the publication of a study in the International Journal of Radiation Oncology, Biology, Physics (Red Journal) demonstrating the ability of the DecisionDx-SCC test to identify high-risk SCC patients who are likely to benefit from ART to reduce metastatic disease progression, as well as high-risk patients who are unlikely to benefit from ART and who, therefore, may consider deferring treatment. This study is the single largest study ever conducted to evaluate the effectiveness of ART in patients diagnosed with SCC and demonstrates the impact of the test in guiding decision-making for recommending ART. See the Company’s news release from May 29, 2024, for more information.
•DecisionDx-SCC: The Company also shared new data that supported the utility of DecisionDx-SCC in patients with high-risk SCC tumors located on the head and neck at the 56th American College of Mohs Surgery (ACMS) Annual Meeting in Phoenix. Data presented demonstrated that testing with DecisionDx-SCC significantly increased the prediction accuracy of metastatic events, when used alone and when combined with National Comprehensive Cancer Network (NCCN) guidelines, Brigham and Women’s Hospital (BWH) staging or American Joint Committee on Cancer Staging Manual, 8th Edition (AJCC8) staging, to better guide risk-aligned patient care decisions regarding metastatic surveillance or the use of adjuvant treatments like radiation. See the Company’s news release from May 3, 2024, for more information.
•DecisionDx-Melanoma: The Company presented new data relating to its DecisionDx-Melanoma test at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, demonstrating the test’s ability to identify patients with localized cutaneous melanoma at the highest risk of metastasis to the central nervous system (CNS). Specifically, the study showed that DecisionDx-Melanoma can identify patients with earlier-stage melanoma who have a higher risk of CNS metastasis within the first three years post-diagnosis. These higher-risk patients may benefit from more frequent imaging surveillance to identify CNS metastases earlier to improve patient survival. See the Company’s news release from May 30, 2024, for more information.
Gastroenterology
•The Company announced that the AGA published new clinical practice guidelines for EET to treat Barrett’s esophagus (BE) and prevent its progression to esophageal adenocarcinoma. These guidelines recognized that there is a high-risk subset of patients with non-dysplastic BE (NDBE) who may benefit from early intervention with EET and acknowledged the role that tissue-based biomarkers, including TissueCypher, can play in identifying these patients. See the Company’s news release from June 24, 2024, for more information.
•The Company also shared three abstracts supporting the ability of its TissueCypher test to predict risk of progression to esophageal cancer in patients with BE at the Digestive Disease Week (DDW) 2024 Annual Meeting in Washington, D.C. The data that was shared further expanded the substantial clinical evidence supporting TissueCypher and its ability to improve the care that BE patients receive. See the Company’s news release from May 14, 2024, for more information.
Mental Health
•The Company was selected as the winner of the "Best Overall Mental Health Solution" award in the eighth annual MedTech Breakthrough Awards program for its IDgenetix pharmacogenomic (PGx) test. The MedTech Breakthrough Awards honor excellence and recognize innovation, hard work and success in a range of health and medical technology categories, attracting thousands of nominations from over 18 countries across the world. See the Company’s news release from May 10, 2024, for more information.
Uveal Melanoma
•The Company announced results from the largest prospective study to date of patients with uveal melanoma, titled "15-Gene Expression Profile and PRAME as Integrated Prognostic Test for Uveal

Melanoma: First Report of Collaborative Ocular Oncology Group Study No. 2 (COOG2.1)," confirming the prognostic accuracy of the DecisionDx-UM test and providing the first prospective validation of Preferentially Expressed Antigen in Melanoma (PRAME) status as a risk refinement tool when considered in the context of a Class 1 or Class 2 DecisionDx-UM result. The study data demonstrated that together, these two tests can guide more precise and risk-aligned decision-making for patients with UM, including referrals, intensity of imaging surveillance and eligibility for ongoing clinical trials. See the Company’s news release from May 8, 2024, and the published paper in the Journal of Clinical Oncology for more information.
Corporate
•The Company announced that its founder, president and chief executive officer, Derek Maetzold, was named by Ernst & Young LLP (EY) as an Entrepreneur Of The Year 2024 Gulf South Award winner. Now in its 38th year, Entrepreneur Of The Year is the preeminent competitive awards program that celebrates entrepreneurs and leaders of high-growth companies who disrupt markets, revolutionize sectors and have a transformational impact on lives. See the Company’s news release from June 14, 2024, for more information.

Conference Call and Webcast Details
Castle Biosciences will hold a conference call on Monday, August 5, 2024, at 4:30 p.m. Eastern time to discuss its second quarter 2024 results and provide a corporate update.

A live webcast of the conference call can be accessed here: View Source
or via the webcast link on the Investor Relations page of the Company’s website,
View Source Please access the webcast at least 10 minutes before the conference call start time. An archive of the webcast will be available on the Company’s website until August 26, 2024.

To access the live conference call via phone, please dial 833 470 1428 from the United States, or +1 404 975 4839 internationally, at least 10 minutes prior to the start of the call, using the conference ID 802518.

There will be a brief Question & Answer session following management commentary.

On August 5, 2024 bioAffinity Technologies, Inc. (Nasdaq: BIAF, BIAFW) reported that pursuant to warrant exercise agreements dated Aug. 2, 2024, three existing accredited investors have exercised outstanding warrants to purchase an aggregate of 1,041,667 of the Company’s shares of common stock ("Existing Warrants") at an exercise price that was reduced from $1.64 to $1.25 per share for gross cash proceeds of approximately $1,302,083 (Press release, BioAffinity Technologies, AUG 5, 2024, View Source [SID1234645354]).

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As part of the transaction, the exercising holders received in a private placement new unregistered warrants ("New Warrants") to purchase up to an aggregate of 1,302,083 shares of common stock (equal to 125% of the shares of common stock issued in connection with the exercise of the Existing Warrants). The New Warrants have an exercise price of $1.50 per share and are initially exercisable on the date that stockholder approval of the exercise of the warrants is obtained and will expire five years from the date of such approval. In connection with the exercise of the Existing Warrants, the Company reduced the exercise price of the Existing Warrants from $1.64 to $1.25 per share.

The Company also announced today it has closed the previously announced securities purchase agreement with an institutional investor for the purchase and sale of 360,000 shares of common stock in a registered direct offering and, in a concurrent private placement, common warrants ("Private Warrants") to purchase up to 450,000 shares of common stock (together with the registered direct offering) at a combined purchase price of $1.25. The Private Warrants have an exercise price of $1.50 per share, are initially exercisable on the date that stockholder approval of the exercise of the warrants is obtained and will expire five years from the date of such approval.

The gross proceeds from the offering are expected to be approximately $450,000, excluding any proceeds that may be received upon the exercise of the Private Warrants and before deducting placement agent fees and other offering expenses payable by the Company.

WallachBeth Capital acted as sole placement agent for the registered direct offering and financial advisor for the warrant inducement transaction.

The common stock was issued in a registered direct offering pursuant to an effective shelf registration statement on Form S-3 (File No. 333-275608) previously filed with the U.S. Securities and Exchange Commission ("SEC"), under the Securities Act of 1933, as amended (the "Securities Act"), and declared effective by the SEC on Nov. 27, 2023. The Private Warrants to be issued in the concurrent private placement and the shares issuable upon exercise of such warrants were offered pursuant to an exemption from the registration requirements of the Securities Act under Section 4(a)(2) thereof and Regulation D promulgated thereunder and have not been registered under the Securities Act or applicable state securities laws. A prospectus supplement describing the terms of the proposed registered direct offering will be filed with the SEC and available on the SEC’s website located at View Source Electronic copies of the prospectus supplements may be obtained, when available, from WallachBeth Capital, LLC, via email at [email protected], by calling +1-646-237-8585, or by standard mail at WallachBeth Capital LLC, Attn: Capital Markets, 185 Hudson St., Suite 1410, Jersey City, NJ 07311, USA.

This press release does not constitute an offer to sell or the solicitation of an offer to buy, nor will there be any sales of these securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of such jurisdiction.

About CyPath Lung

CyPath Lung uses advanced flow cytometry and artificial intelligence (AI) to identify cell populations in patient sputum that indicate malignancy. Automated data analysis helps determine if cancer is present or if the patient is cancer-free. CyPath Lung incorporates a fluorescent porphyrin, TCPP, that is preferentially taken up by cancer and cancer-related cells. Clinical study results demonstrated that CyPath Lung had 92% sensitivity, 87% specificity and 88% accuracy in detecting lung cancer in patients at high risk for the disease who had small lung nodules less than 20 millimeters. Diagnosing and treating early-stage cancer can improve outcomes and increase patient survival.

On August 5, 2024 CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, reported financial results for the second quarter ended June 30, 2024 (Press release, CRISPR Therapeutics, AUG 5, 2024, View Source [SID1234645336]).

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"In addition to the continued momentum of CASGEVY’s launch, we are making significant progress across the rest of our pipeline," said Samarth Kulkarni, Ph.D., Chief Executive Officer and Chairman of CRISPR Therapeutics. "We continue to advance our next generation CD19-directed CAR T cell program, CTX112, which has the potential to be best-in-class in both oncology and autoimmune indications. We have opened the clinical trial for CTX131 in hematologic malignancies, and continue to dose-escalate with our in vivo directed programs, CTX310 and CTX320. We are making outstanding progress across our early stage discovery efforts and are well-positioned to realize our mission of bringing multiple transformative medicines to patients in need."

Recent Highlights and Outlook

Hemoglobinopathies and CASGEVY (exagamglogene autotemcel [exa-cel])

CRISPR Therapeutics has two next generation approaches with the potential to significantly expand the addressable population with SCD and TDT. The Company continues to advance its internally developed targeted conditioning program, an anti-CD117 (c-Kit) antibody-drug conjugate (ADC), through preclinical studies. Additionally, the Company has ongoing research efforts to enable in vivo editing of hematopoietic stem cells. This work could obviate the need for conditioning altogether, expand geographic reach, and enable the treatment of multiple additional other diseases beyond SCD and TDT.
Enrollment has been completed in two global Phase 3 studies of CASGEVY in people 5 to 11 years of age with SCD or TDT and the trials are ongoing.
In June, positive long-term data from CLIMB-111, CLIMB-121 and the long-term follow-up study of CASGEVY were presented at the 2024 Annual European Hematology Association (EHA) (Free EHA Whitepaper) Congress. These long-term data from more than 100 patients dosed with CASGEVY, with the longest follow-up of more than five years, confirm the transformative, consistent, and durable clinical benefits of CASGEVY over time.
The French National Authority for Health (HAS) approved Vertex’s request for the implementation of an early access program (EAP) for the use of CASGEVY in indicated patients with SCD. HAS previously approved the implementation of an EAP for CASGEVY in indicated patients with TDT in the first quarter of 2024.
As of mid-July, more than 35 authorized treatment centers (ATCs) have been activated globally, including centers in all regions where CASGEVY is approved, and approximately 20 patients have had cells collected across all regions.
CASGEVY is approved in the U.S., Great Britain, the European Union (EU), the Kingdom of Saudi Arabia (KSA), and the Kingdom of Bahrain (Bahrain) for the treatment of both sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT), and launches are ongoing. Regulatory submissions for CASGEVY have been completed in both SCD and TDT in Switzerland and Canada where it received Priority Review. CASGEVY is the first therapy to emerge from a strategic partnership between CRISPR Therapeutics and Vertex Pharmaceuticals established in 2015. As part of an amendment to the collaboration agreement in 2021, Vertex now leads global development, manufacturing, regulatory and commercialization of CASGEVY with support from CRISPR Therapeutics.
Immuno-Oncology and Autoimmune Diseases

CTX131 is currently in an ongoing clinical trial in solid tumors. In addition, the Company has opened a clinical trial for CTX131 in hematologic malignancies including T cell lymphomas (TCL). Allogeneic CAR T approaches for TCL may have greater potential to meet the unmet need in this patient population given the patients’ own T cells are not suitable for autologous manufacturing.
CRISPR Therapeutics opened a clinical trial for CTX112 in systemic lupus erythematosus (SLE), with the potential to expand into additional autoimmune indications in the future. Early clinical studies conducted by third parties have shown that CD19-directed autologous CAR T therapy can produce long-lasting remissions in multiple autoimmune indications by deeply depleting B cells. The Company’s first generation allogeneic CD19-directed CAR T program has demonstrated effective depletion of B cells in oncology settings, which supports the potential for CTX112 in autoimmune diseases.
CTX112 is being developed for both oncology and autoimmune indications. In oncology settings, CTX112 is in a Phase 1/2 trial for CD19 positive relapsed or refractory B-cell malignancies, and the Company expects to report preliminary clinical data this year.
CRISPR Therapeutics’ next generation allogeneic CAR T candidates reflect the Company’s mission of innovating continuously to bring potentially transformative medicines to patients as quickly as possible. Clinical trials are ongoing for the Company’s next generation CAR T product candidates, CTX112 and CTX131, targeting CD19 and CD70, respectively, across multiple indications. CTX112 and CTX131 both contain novel potency edits which can lead to significantly higher CAR T cell expansion and cytotoxicity, potentially representing best-in-class allogeneic CAR T products for these targets.
In Vivo

CRISPR Therapeutics has established a proprietary lipid nanoparticle (LNP) platform for the delivery of CRISPR/Cas9 to the liver. The first two in vivo programs utilizing this proprietary platform, CTX310 and CTX320, are directed towards validated therapeutic targets associated with cardiovascular disease.
CTX310 is currently in an ongoing Phase 1 trial targeting ANGPTL3 in patients with homozygous familial hypercholesterolemia (HoFH), severe hypertriglyceridemia (SHTG), heterozygous familial hypercholesterolemia (HeFH), or mixed dyslipidemias. Natural loss-of-function mutations in ANGPTL3 are associated with reduced low-density lipoprotein (LDL-C), triglycerides (TG) and atherosclerotic cardiovascular disease (ASCVD) risk without any negative impact on overall health.
CTX320 is currently in an ongoing Phase 1 trial targeting LPA in patients with elevated lipoprotein(a) [Lp(a)], which has shown to have an independent association with major adverse cardiovascular events (MACE). Up to 20% of the global population has elevated Lp(a) levels.
The Company continues to advance two additional preclinical programs, CTX340 targeting angiotensinogen (AGT) for the treatment of refractory hypertension and CTX450 targeting 5’ aminolevulinic acid synthase (ALAS1) for the treatment of acute hepatic porphyrias (AHP). CRISPR Therapeutics has initiated IND/CTA-enabling studies for CTX340, targeting hepatic AGT for hypertension, and expects to initiate both clinical trials in the second half of 2025.
Regenerative Medicine

CTX211, an allogeneic, gene-edited, stem cell-derived beta islet cell precursor, is currently in an ongoing Phase 1 clinical trial for the treatment of Type 1 Diabetes (T1D). CRISPR Therapeutics remains committed to its goal of developing a beta-cell replacement product that does not require chronic immunosuppression.
Vertex has non-exclusive rights to certain CRISPR Therapeutics’ CRISPR/Cas9 technology to accelerate development of potentially curative cell therapies for T1D. CRISPR Therapeutics remains eligible for development milestones and would receive royalties on any future products resulting from this agreement.
Other Corporate Matters

In May, CRISPR Therapeutics announced the appointment of Naimish Patel, M.D., as Chief Medical Officer. Dr. Patel brings in-depth experience in successfully accelerating innovation and advancing drug candidates across a breadth of modalities and disease areas. Dr. Patel is an experienced drug developer who has worked across a wide range of disease areas, including his most recent leadership role as the Global Development Therapeutic Area Head of Immunology and Inflammation at Sanofi. In addition, the Company announced the promotions of (i) Julianne Bruno, M.B.A., to Chief Operating Officer; Ms. Bruno previously served as the Company’s Senior Vice President and Head of Programs & Portfolio Management; and (ii) Susan Kim to Senior Vice President, Investor Relations and Corporate Communications; Ms. Kim previously served as the Company’s Vice President of Investor Relations and Corporate Communications.
Second Quarter 2024 Financial Results

Cash Position: Cash, cash equivalents, and marketable securities were $2,012.8 million as of June 30, 2024, compared to $1,695.7 million as of December 31, 2023. The increase in cash was primarily driven by proceeds from the $280.0 million February 2024 registered direct offering, a $200.0 million milestone payment received from Vertex in connection with the approval of CASGEVY, proceeds from employee option exercises as well as interest income, offset by operating expenses.
Revenue: Total collaboration revenue for the second quarter of 2024 was not material. Collaboration revenue for the second quarter of 2023 was $70.0 million. Collaboration revenue recognized in the second quarter of 2023 was primarily attributable to a research milestone achieved during the current quarter in connection with a non-exclusive license agreement with Vertex.
R&D Expenses: R&D expenses were $80.2 million for the second quarter of 2024, compared to $101.6 million for the second quarter of 2023. The decrease in R&D expense was primarily driven by reduced variable external research and manufacturing costs.
G&A Expenses: General and administrative expenses were $19.5 million for the second quarter of 2024, compared to $19.0 million for the second quarter of 2023.
Collaboration Expense: Collaboration expense, net, was $52.1 million for the second quarter of 2024, compared to $44.6 million for the second quarter of 2023. The increase in collaboration expense, net, was primarily attributable to manufacturing and commercial costs under the CASGEVY collaboration with Vertex.
Net Loss: Net loss was $126.4 million for the second quarter of 2024, compared to a net loss of $77.7 million for the second quarter of 2023.
About CASGEVY (exagamglogene autotemcel [exa-cel])
CASGEVY is a non-viral, ex vivo CRISPR/Cas9 gene-edited cell therapy for eligible patients with SCD or TDT, in which a patient’s own hematopoietic stem and progenitor cells are edited at the erythroid specific enhancer region of the BCL11A gene. This edit results in the production of high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is the form of the oxygen-carrying hemoglobin that is naturally present during fetal development, which then switches to the adult form of hemoglobin after birth. CASGEVY has been shown to reduce or eliminate VOCs for patients with SCD and transfusion requirements for patients with TDT. CASGEVY is approved for certain indications in multiple jurisdictions for eligible patients.

On August 5, 2024 Nuvation Bio Inc. (NYSE: NUVB), a late clinical-stage, global biopharmaceutical company tackling some of the greatest unmet needs in oncology, reported financial results for the second quarter ended June 30, 2024, and provided a business update (Press release, Nuvation Bio, AUG 5, 2024, View Source [SID1234645355]).

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"In the second quarter, we were pleased to share data at ASCO (Free ASCO Whitepaper) from TRUST-I, the pivotal study of taletrectinib in China, which although immature due to an early data cutoff, demonstrated taletrectinib’s efficacy, durability, and safety profiles. At WCLC, we will be presenting data from TRUST-II, the global, pivotal Phase 2 study of taletrectinib, while at ESMO (Free ESMO Whitepaper) we will present more mature and comprehensive taletrectinib data, including pooled efficacy and safety data from both pivotal TRUST-I and TRUST-II studies. The ESMO (Free ESMO Whitepaper) data set will be used to support our planned NDA filing in the U.S. and, assuming regulatory approval, will position us to commercialize taletrectinib in 2025," said David Hung, M.D., Founder, President, and Chief Executive Officer of Nuvation Bio. "We are also progressing the global Phase 2 study of safusidenib and continuing to dose escalate in a Phase 1/2 study of our first clinical-stage drug-drug conjugate, NUV-1511. As we focus on our late-stage pipeline and prepare to potentially bring taletrectinib to patients in the U.S. in 2025, we have decided not to initiate a Phase 2 study of NUV-868 in the solid tumor indications studied to date. This decision comes after careful review of the data generated in the Phase 1 monotherapy study and Phase 1b study of NUV-868 in combination with olaparib or enzalutamide. We are exploring next steps for NUV-868 in new indications and will share updates as available. We are proud of Nuvation Bio’s transformational momentum in the first half of this year and look forward to building upon it as we tackle some of the greatest unmet needs in oncology."

Recent Pipeline Updates:

Taletrectinib, ROS1 inhibitor: Advanced ROS1-positive NSCLC

Latest data from the Phase 2 TRUST-I clinical study evaluating taletrectinib in patients in China with advanced ROS1-positive NSCLC was published in the Journal of Clinical Oncology and presented at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting.
Latest pooled data from the pivotal Phase 2 TRUST-I and TRUST-II studies to be presented at the ESMO (Free ESMO Whitepaper) Congress 2024 in September, which will support the Company’s planned NDA in the U.S.
Latest data from the global, pivotal Phase 2 TRUST-II study to be presented at the WCLC in September.
Granted Orphan Drug Designation by the U.S. FDA for the treatment of ROS1-positive NSCLC and other NSCLC indications.
Safusidenib, mIDH1 inhibitor: Diffuse IDH1-mutant glioma

Global phase 2 study of safusidenib for treatment of patients with diffuse IDH1-mutant glioma remains ongoing.
NUV-1511, drug-drug conjugate (DDC): Advanced solid tumors

Phase 1/2 dose escalation study of NUV-1511 for the treatment of patients with various advanced solid tumors remains ongoing.
NUV-868, BD2-selective BET inhibitor: Advanced solid tumors

Concluded the Phase 1b dose escalation study of NUV-868 in combination with olaparib for the treatment of patients with ovarian cancer, pancreatic cancer, metastatic castration-resistant prostate cancer (mCRPC), triple negative breast cancer, and other solid tumors, and in combination with enzalutamide for the treatment of patients with mCRPC.
Completed an internal analysis of efficacy and safety data collected from the Phase 1 monotherapy and Phase 1b combination studies of NUV-868. Following this analysis, Nuvation Bio decided not to initiate a Phase 2 study of NUV-868 as a monotherapy or in combination with olaparib or enzalutamide in the advanced solid tumor indications that were part of the Phase 1 and Phase 1b study designs. The Company is evaluating next steps for the NUV-868 program, including further development in combination with approved products for indications in which BD2-selective BET inhibitors may improve outcomes for patients.
Second Quarter 2024 Financial Results

As of June 30, 2024, Nuvation Bio had cash, cash equivalents and marketable securities of $577.2 million.

For the three months ended June 30, 2024, research and development expenses were $29.2 million, compared to $18.6 million for the three months ended June 30, 2023. The increase was primarily due to a $5.9 million increase in personnel-related costs driven by the acquisition of AnHeart Therapeutics, Ltd. (AnHeart), stock-based compensation and other benefits and a $4.7 million increase in third-party costs related to research services and drug manufacturing as a result of clinical study expense for taletrectinib.

On April 9, 2024, as a result of the acquisition of AnHeart, Nuvation Bio recorded a $425.1 million charge representing an acquired in-process research and development asset with no alternative future use in acquired in-process research and development expenses.

For the three months ended June 30, 2024, general and administrative expenses were $16.1 million, compared to $7.5 million for the three months ended June 30, 2023. The increase was due to a $3.9 million increase in personnel-related costs as a result of the acquisition of AnHeart, a $1.1 million increase in professional fees, a $1.2 million increase in marketing expense, a $0.8 million increase in legal fees, a $0.2 million increase in occupancy expense, a $0.2 million increase in foreign currency impact, and a $1.4 million increase in miscellaneous expense offset by a $0.2 million decrease in insurance expense.

For the three months ended June 30, 2024, Nuvation Bio reported a net loss of $462.5 million, or $(1.89) per share. This compares to a net loss of $20.6 million, or $(0.09) per share, for the comparable period in 2023.

About Taletrectinib

Taletrectinib is an oral, potent, central nervous system-active, selective, next-generation ROS1 inhibitor specifically designed for the treatment of patients with ROS1-positive non-small cell lung cancer (NSCLC). Taletrectinib is being evaluated for the treatment of patients with advanced ROS1-positive NSCLC in two Phase 2 single-arm pivotal studies: TRUST-I (NCT04395677) in China, and TRUST-II (NCT04919811), a global study. Taletrectinib has been granted Orphan Drug Designation by the U.S. FDA for the treatment of patients with ROS1-positive NSCLC and Breakthrough Therapy Designations by both the U.S. FDA and China’s National Medical Products Administration (NMPA) for the treatment of patients with advanced or metastatic ROS1-positive NSCLC. Based on results of the TRUST-I clinical study, China’s NMPA has accepted and granted Priority Review Designations to New Drug Applications for taletrectinib for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC who either have or have not previously been treated with ROS1 tyrosine kinase inhibitors.