On August 8, 2024 Citius Pharmaceuticals, Inc. (NASDAQ: CTXR) ("Citius", "Citius Pharma"), reported that the U.S. Food and Drug Administration (FDA) has approved LYMPHIR (denileukin diftitox-cxdl), a novel immunotherapy for the treatment of r/r cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy (Press release, Citius Pharmaceuticals, AUG 8, 2024, View Source [SID1234645590]). LYMPHIR is the only CTCL therapy that targets the interleukin-2 (IL-2) receptor found on malignant T-cells and Tregs. This is the first indication for LYMPHIR and the first FDA-approved product for Citius Pharma.

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"LYMPHIR offers new hope for patients suffering from cutaneous T-cell lymphoma, a rare and chronic cancer characterized by debilitating skin lesions and severe itching. This approval is a significant milestone for CTCL patients. The introduction of LYMPHIR, with its potential to rapidly reduce skin disease and control symptomatic itching without cumulative toxicity, is expected to expand the CTCL treatment landscape and grow the overall market, currently estimated to be $300-$400 million," stated Leonard Mazur, Chief Executive Officer of Citius Pharmaceuticals.

"LYMPHIR, with an initial indication in the treatment of CTCL, is the first of our pipeline candidates to receive FDA approval. Citius is dedicated to working closely with healthcare providers to ensure that all r/r CTCL patients have timely access to this important new therapy. We are preparing to launch LYMPHIR in the U.S. market within the next five months," added Mazur.

"We are grateful to the clinicians, patients, and researchers who contributed to the development of LYMPHIR. We believe LYMPHIR’s unique IL-2 receptor-targeted treatment, which kills tumor cells directly, and concurrently depletes host Tregs in order to boost the body’s immune response, is an important differentiator and offers clinically meaningful benefits to a significant percentage of r/r patients. As the only IL-2 receptor-targeted immunotherapy for CTCL, LYMPHIR provides a novel and non-cross-resistant treatment option without cumulative toxicity for Stage I-III r/r patients for whom symptomatic skin involvement interferes with their daily quality of life. LYMPHIR’s median time-to-response of only 1.4 months (min, max: 0.7, 5.6) offers many patients rapid skin relief," added Dr. Myron Czuczman, Chief Medical Officer of Citius Pharmaceuticals.

CTCL is a rare and often debilitating chronic non-Hodgkin lymphoma that primarily affects the skin. Approximately 2,500-3,000 patients are diagnosed each year with an estimated 40,000 living with the disease. Patients with r/r CTCL have limited treatment options. No universally defined single treatment is used to treat these patients with incurable cancer. Patients typically cycle through several skin-directed therapies before the cancer becomes resistant and/or progressive at which point systemic agents are needed to achieve effective disease control. Reducing and controlling skin plaques and itching without cumulative toxicity is a primary goal of CTCL treatment. Systemic medicines are prescribed until the disease progresses again or when dose-limiting toxicity occurs, after which HCPs prescribe a different systemic medicine. LYMPHIR provides another viable option in the treatment landscape with unique benefits to patients. It offers a novel mechanism of action designed to target and eradicate malignant T-cells while preserving healthy tissue. It is the only treatment option that targets the IL-2 receptors found in T-cell lymphomas and Tregs.

"As a treating oncologist, I have seen the profound negative effect on the quality of life in patients with r/r CTCL. Given the long-term nature of the disease, pruritus, ulceration of the tumors, and secondary pyogenic skin infection, it is vital to get this skin involvement under control. LYMPHIR is the first therapeutic option in many years to offer hope of reducing skin disease, bringing us one step closer to filling the need for CTCL patients, particularly those that are not able to complete or continue prior therapies," stated Dr. Francine Foss, Professor of Hematology, and Director of the Multidisciplinary T-cell Lymphoma Program at Yale Cancer Center, New Haven, CT.

The approval of LYMPHIR is based on results from the Phase 3 Pivotal Study 302 (NCT01871727) of CTCL patients who had previously received at least one systemic treatment. Actual study patients received a median of 4 (min, max: 1, 18) prior anticancer therapies. The primary efficacy population includes 69 patients with stage I-III CTCL who were treated with denileukin diftitox-cxdl (9 μg /kg/day). The primary efficacy outcome measure was Objective Response Rate (ORR), as assessed by an Independent Review Committee (IRC). The ORR was 36.2%, (95% CI: 25.0-48.7), with 8.7% achieving a Complete Response (CR).

The median time to response was rapid at 1.41 months, with the majority of responders (~70%) seeing results after 1–2 cycles of treatment. Duration of response was at least 6 months for 52.0% of the patients. 84.4% (54/64) of skin evaluable subjects had a decrease in skin tumor burden and 12.5% (8/64) saw complete clearing of skin disease. Pruritis was evaluated as an exploratory endpoint with 31.7% of patients demonstrating clinically significant pruritus improvement. Importantly, no cumulative toxicity was observed in patients receiving LYMPHIR.

LYMPHIR’s safety profile is consistent with the known safety profile for denileukin diftitox. Across three studies of 119 CTCL patients receiving 9 μg dose of denileukin diftitox, the most common (≥20%) adverse reactions, including laboratory abnormalities, were increased transaminases, albumin decreased, nausea, edema, hemoglobin decreased, fatigue, musculoskeletal pain, rash, chills, constipation, pyrexia, and capillary leak syndrome (CLS).

The U.S. Prescribing Information for LYMPHIR contains a boxed warning that CLS, including life-threatening or fatal reactions, can occur in patients receiving LYMPHIR. Monitor patients for signs and symptoms of CLS during treatment. Withhold LYMPHIR until CLS resolves, or permanently discontinue based on severity. Additional "Important Safety Information" is available below and LYMPHIR’s full prescribing information may be accessed here in the next few days.

This approval includes a postmarketing requirement from the FDA to characterize the risk of visual impairment in CTCL patients treated with LYMPHIR. Citius is committed to the safety of patients and will continue to monitor all safety data as it emerges.

About Study 302

The efficacy of LYMPHIR was evaluated in Study 302, an open-label, single-arm, multicenter trial in patients with r/r Stage I to IV CTCL. Eligible patients were required to have expression of CD25 on ≥ 20% of biopsied malignant cells by immunohistochemistry. The study excluded patients with significant cardiac disease or uncontrolled infections. Patients received LYMPHIR at 9 mcg/kg as an intravenous infusion daily from Day 1 through Day 5 of each 21-day cycle. Patients continued to receive LYMPHIR until disease progression or unacceptable toxicity.

The efficacy population includes 69 patients with r/r Stage I to III CTCL. Of the 69 patients, the median age was 64 years (range: 28 to 87 years), 65% were male, 73% were White, 19% Black or African American, 1% Asian, and 14% Hispanic or Latino. The CTCL disease stage was IA in 7%, IB in 23%, IIA in 13%, IIB in 35%, IIIA in 12%, and IIIB in 10%. The median number of prior therapies was 4 (range: 1 to 18), including both skin-directed and systemic therapies. Prior therapies included photodynamic therapy (56%), total skin electron beam therapy (42%), systemic retinoids (49%), methotrexate/pralatrexate (49%), histone deacetylase inhibitor (35%), brentuximab vedotin (26%) and mogamulizumab (12%).

Efficacy was established based on ORR, according to ISCL/EORTC Global Response Score (GRS) per Independent Review Committee (Olsen 2011). Efficacy results are shown in the table below.

Table: Efficacy Results of Study 302

Efficacy Endpoint
LYMPHIR

9 mcg/kg/day

(N=69)

ORR (GRS)%a

36%

(95% CIb) (25, 49)
Complete Response 9%
Partial Response 27%
Duration of Responsec
Range, months 3.0+, 23.5+
Duration ≥ 6 months, n (%) 13 (52%)
Duration ≥ 12 months, n (%) 5 (20%)

a ORR, objective response rate per Olsen, et al (2011) Global Response Score (GRS), by Independent Review Committee (IRC).
b CI, confidence interval
c The median (95% CI) DOR using Kaplan-Meier (KM) estimate was not estimable (NE) among the 25 subjects due to censoring.

Median time to response was 1.4 months (range: 0.7 to 5.6 months).

Among responders, the median follow-up for duration of response was 6.5 months (range: 3.5+, 23.5+ months).

About LYMPHIR (denileukin diftitox-cxdl)

LYMPHIR is a targeted immune therapy for r/r (R/R) CTCL indicated for use in Stage I-III disease after at least one prior systemic therapy. It is a recombinant fusion protein that combines the IL-2 receptor binding domain with diphtheria toxin fragments. The agent specifically binds to IL-2 receptors on the cell surface, causing diphtheria toxin fragments that have entered cells to inhibit protein synthesis. After uptake into the cell, the DT fragment is cleaved and the free DT fragments inhibit protein synthesis, resulting in cell death. Denileukin diftitox-cxdl demonstrated the ability to deplete immunosuppressive regulatory T lymphocytes (Tregs) and antitumor activity through a direct cytocidal action on IL-2R-expressing tumors.

In 2021, denileukin diftitox received regulatory approval in Japan for the treatment of CTCL and PTCL. Subsequently, in 2021, Citius acquired an exclusive license with rights to develop and commercialize LYMPHIR in all markets except for Japan and certain parts of Asia.

About Cutaneous T-cell Lymphoma

Cutaneous T-cell lymphoma is a type of cutaneous non-Hodgkin lymphoma (NHL) that comes in a variety of forms and is the most common type of cutaneous lymphoma. In CTCL, T-cells, a type of lymphocyte that plays a role in the immune system, become cancerous and develop into skin lesions, leading to a decrease in the quality of life of patients with this disease due to severe pain and pruritus. Mycosis Fungoides (MF) and Sézary Syndrome (SS) comprise the majority of CTCL cases. Depending on the type of CTCL, the disease may progress slowly and can take anywhere from several years to upwards of ten to potentially reach tumor stage. However, once the disease reaches this stage, the cancer is highly malignant and can spread to the lymph nodes and internal organs, resulting in a poor prognosis. Given the duration of the disease, patients typically cycle through multiple agents to control disease progression. CTCL affects men twice as often as women and is typically first diagnosed in patients between the ages of 50 and 60 years of age. Other than allogeneic stem cell transplantation, for which only a small fraction of patients qualify, there is currently no curative therapy for advanced CTCL.

INDICATION

LYMPHIR is an IL2-receptor-directed cytotoxin indicated for the treatment of adult patients with r/r Stage I-III cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy.

IMPORTANT SAFETY INFORMATION

BOXED WARNING: CAPILLARY LEAK SYNDROME

Capillary leak syndrome (CLS), including life-threatening or fatal reactions, can occur in patients receiving LYMPHIR. Monitor patients for signs and symptoms of CLS during treatment. Withhold LYMPHIR until CLS resolves, or permanently discontinue based on severity.

WARNINGS AND PRECAUTIONS

Capillary Leak Syndrome

LYMPHIR can cause capillary leak syndrome (CLS), including life-threatening or fatal reactions. CLS was defined in the clinical trials as the occurrence of at least 2 of the following symptoms at any time during LYMPHIR therapy: hypotension, edema, and serum albumin <3 g/dL. These symptoms were not required to occur simultaneously to be characterized as capillary leak syndrome.

As defined, CLS occurred in 27% of patients in the pooled population across 3 clinical trials, including 8% with Grade 3. There was one (0.8%) fatal occurrence of CLS. Of the patients with CLS, 22% had recurrence. The majority of CLS events (81%) occurred within the first 2 cycles of treatment. The median time to onset from Cycle 1, Day 1 was 6.5 days (range: 1 to 77), the median duration of CLS was 14 days (range: 2 to 40), and 75% of patients had resolution. The most common symptoms included edema, hypoalbuminemia, and hypotension. Pleural effusion, pericardial effusion, and dehydration also occurred.

Regularly assess patients for weight gain, new onset or worsening of edema, dyspnea, and hypotension (including orthostatic changes). Monitor serum albumin levels prior to the initiation of each cycle of therapy and more often as clinically indicated.

Withhold, reduce dose, or permanently discontinue based on severity. If LYMPHIR is withheld, resume LYMPHIR following resolution of CLS and when serum albumin is greater than or equal to 3 g/dL.

Visual Impairment

LYMPHIR can cause serious visual impairment, including changes in visual acuity and color vision. In the pooled population across 3 clinical trials, visual impairment occurred in 9%, with Grade 1 in 8% and Grade 2 in 1%. The most commonly reported symptom was blurred vision. Of the patients with visual impairment, 67% had resolution of their visual impairment.

Perform baseline ophthalmic examination and monitor as clinically indicated. If patients experience symptoms of visual impairment, such as changes in visual acuity, changes in color vision, or blurred vision, refer for ophthalmologic evaluation.

Withhold LYMPHIR until visual impairment resolves or permanently discontinue based on severity.

Infusion-Related Reactions

LYMPHIR can cause serious infusion-related reactions. Infusion-related reactions were reported in 69% of patients in the pooled population across 3 clinical trials of patients who received LYMPHIR, with Grade 3 infusion-related reactions in 3.4% [see Adverse Reactions (6.1)]. Eighty-three percent of infusion-related reactions occurred in Cycles 1 and 2. The most common symptoms included nausea, fatigue, chills, musculoskeletal pain, vomiting, fever, and arthralgia.

Premedicate patients for the first three cycles prior to starting a LYMPHIR infusion [see Dosage and Administration (2.3)]. Monitor patients frequently during infusion. For Grade 2 or higher infusion reactions, premedicate at least 30 minutes prior to each subsequent infusion with a systemic steroid for at least 3 cycles.

Interrupt or discontinue LYMPHIR based on severity [see Dosage and Administration (2.4)]. Institute appropriate medical management.

Hepatotoxicity

LYMPHIR can cause hepatotoxicity. In the pooled safety population, elevated ALT occurred in 70% of patients, with Grade 3 ALT occurring in 22%; elevated AST occurred in 64% of patients, with Grade 3 AST elevation occurring in 9%. For Grade 3 events, median time to onset was 8 days (range: 1 to 15 days); median time to resolution was 15 days (range: 7 to 50 days); all cases of Grade 3 ALT or AST elevations resolved [see Adverse Reactions (6.1)]. Elevated total bilirubin occurred in 5% of patients, with Grade 3 occurring in 0.9%.

Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold, reduce dose, or permanently discontinue LYMPHIR based on severity.

Embryo-Fetal Toxicity

Based on its mechanism of action, LYMPHIR can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to the initiation of LYMPHIR. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment and for 7 days following the last dose of LYMPHIR.

ADVERSE REACTIONS

The most common adverse reactions (≥20%), including laboratory abnormalities, are increased transaminases, albumin decreased, nausea, edema, hemoglobin decreased, fatigue, musculoskeletal pain, rash, chills, constipation, pyrexia, and capillary leak syndrome

USE IN SPECIFIC POPULATIONS

Pregnancy

Risk Summary

Based on its mechanism of action, LYMPHIR can cause fetal harm when administered to a pregnant woman. There are no available data on the use of LYMPHIR in pregnant women to evaluate for a drug-associated risk. No animal reproductive and developmental toxicity studies have been conducted with denileukin diftitox.

Denileukin diftitox-cxdl causes depletion of regulatory T lymphocytes (Treg), immune activation, and capillary leak syndrome, compromising pregnancy maintenance. Advise pregnant women of the potential risk to a fetus.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies are 2-4% and 15-20%, respectively.

Lactation

Risk Summary

No data are available regarding the presence of denileukin diftitox-cxdl in human milk, the effects on the breastfed child, or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with LYMPHIR and for 7 days after the last dose.

Females and Males of Reproductive Potential

Based on its mechanism of action, LYMPHIR can cause fetal harm when administered to a pregnant woman.

Pregnancy Testing

Verify the pregnancy status of females of reproductive potential prior to initiating LYMPHIR.

Contraception

Females

Advise females of reproductive potential to use effective contraception during treatment with LYMPHIR and for 7 days after the last dose.

Infertility

Males

Based on findings in rats, male fertility may be compromised by treatment with. The reversibility of the effect on fertility is unknown.

Pediatric Use

Safety and effectiveness of LYMPHIR in pediatric patients have not been established.

Geriatric Use

Of the 69 patients with Stage I-III r/r CTCL who received LYMPHIR, 34 patients (49%) were 65 years of age and older and 10 patients (14%) were 75 years of age and older. Clinical studies of LYMPHIR did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients.

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Citius Pharmaceuticals at 1-844-459-6744.

Please read Important Safety Information and full Prescribing Information, including Boxed WARNING, for LYMPHIR which will be available in the next few days

On August 8, 2024 Century Therapeutics, Inc. (NASDAQ: IPSC), an innovative biotechnology company developing induced pluripotent stem cell (iPSC)-derived cell therapies in immuno-oncology and autoimmune disease, reported financial results and business highlights for the second quarter ended June 30, 2024 (Press release, Century Therapeutics, AUG 8, 2024, View Source [SID1234645589]).

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"Our strategic autoimmune expansion, as highlighted by the recent initiation of the CALiPSO-1 trial in Systemic Lupus Erythematosus and addition of a Lupus Nephritis-specific cohort, positions Century as a potential leader in allogeneic cell therapies for autoimmune diseases. 2024 remains a time of focused execution as we work to advance our next-generation allogeneic iPSC-derived cell therapy platform and pipeline, equipped with our proprietary Allo-Evasion technology, capturing a diversified opportunity to address a broad range of indications with high unmet need. I am proud of the significant progress we have achieved in such a short period of time, particularly underscored by the evolution of our platform and capabilities, which we anticipate will enable our iPSC candidates to have a more controlled, durable, and tolerable profile," said Brent Pfeiffenberger, Pharm.D., Chief Executive Officer of Century Therapeutics. "We remain focused on progressing CNTY-101 in both of our clinical-stage programs, including advancement into dose expansion in the ELiPSE-1 trial in patients with r/r B-cell lymphomas and acceleration of patient enrollment following the recent initiation of the CALiPSO-1 trial. We’ve made strides in our initial execution of autoimmune expansion as evidenced by our CALiPSO-1 trial updates, while simultaneously pursuing additional regulatory filings for CNTY-101 in other autoimmune disease indications in the second half of the year. We look forward to continued execution and the opportunity to deliver on our next set of potential catalysts, including the expectation of initial clinical data from CALiPSO-1 by year-end."

Research & Development Highlights

· Consistent with Century’s autoimmune disease expansion efforts announced in April 2024, the Company recently initiated the Phase 1 CALiPSO-1 trial of CNTY-101 (NCT06255028) in Systemic Lupus Erythematosus (SLE). The first clinical trial site has been activated, with additional sites continuing to open across the United States. The Company expects initial clinical data from CALiPSO-1 by year-end 2024. Furthermore, Century recently amended the protocol to include a new indication-specific cohort of Lupus Nephritis (LN) patients. CALiPSO-1 is an open-label multi-center clinical trial to evaluate the safety, tolerability, pharmacokinetics, and clinical response of CNTY-101 in patients with moderate to severe SLE and LN who have failed at least two standard immunosuppressive therapies. The inclusion of LN patients highlights Century’s execution in pursuing additional regulatory filings as a way of accelerating and broadening its research and development initiatives in autoimmune diseases. The Company intends to submit additional regulatory filings for CNTY-101 in autoimmune disease indications with limited current treatment options and high unmet need in the second half of 2024.

· In May 2024, Century presented two posters at the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) Annual Meeting showcasing the potential ability of its lead program, CNTY-101, a CD19 targeting allogeneic iNK cell therapy with 6 precision gene edits powered by Century’s Allo-Evasion technology, to treat B-Cell driven autoimmune diseases including SLE, and new preclinical data demonstrating the potential utility of using a novel synthetic ligand targeting CD300a as a universal strategy for preventing natural killer (NK) cell mediated rejection in allogeneic cell therapies. The Company believes that these capabilities demonstrate the potential protection of allogeneic cell therapies with the possibility for improved outcomes, while delivering a broadly beneficial treatment option across a range of indications.

· In June 2024, the Company presented encouraging interim efficacy and safety data from the ongoing Phase 1 ELiPSE-1, multicenter, open-label clinical trial of CNTY-101 (NCT05336409) in heavily pre-treated patients with R/R CD19-positive B-cell lymphomas at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. Evaluable preliminary safety (n=12) and efficacy (n=10) as of the data cutoff date of March 27, 2024, from the ongoing dose escalation portion of the trial, demonstrated a manageable tolerability profile with no observed dose limiting toxicities (DLT) or graft-versus-host disease (GvHD). After rapidly trafficking out of circulation, pharmacokinetics (PK), evaluated by a novel cell-free DNA method, showed that CNTY-101 persistence outside the bloodstream trended with increases in dose. Data also showed additional responses across escalating doses and different types of B-cell malignancies in heavily pretreated patients with predominantly aggressive or high-risk histologies.

· The Company recently completed dose escalation of schedule A (single dose per cycle) and schedule B (3 doses per cycle) in the ELiPSE-1 trial and is currently enrolling patients in the dose confirmation portion. Progression into dose expansion is expected in the second half of 2024.

Corporate Highlights

· In April 2024, the Company completed a private placement of common stock with gross proceeds of $60 million with new and existing investors. Also in April 2024, the Company closed the acquisition of Clade Therapeutics, bringing enhancement of its Allo-Evasion platform and adding three preclinical stage αβ iT programs spanning across cancer and autoimmune diseases to its pipeline.

Second Quarter 2024 Financial Results

· Cash Position: Cash, cash equivalents, and marketable securities were $269.6 million as of June 30, 2024, as compared to $261.8 million as of December 31, 2023. Net cash used in operations was $57.6 million for the six months ended June 30, 2024, compared to net cash used in operations of $48.5 million for the six months ended June 30, 2023.

· Collaboration Revenue: Collaboration revenue generated through the Company’s collaboration, option, and license agreement with Bristol-Myers Squibb was $0.8 million for the three months ended June 30, 2024, compared to $0.1 million for the same period in 2023.

· Research and Development (R&D) expenses: R&D expenses were $27.2 million for the three months ended June 30, 2024, compared to $22.7 million for the same period in 2023. The increase in R&D expenses was primarily due to increased manufacturing activity for CNTY-101 and the acquisition of Clade Therapeutics.

· General and Administrative (G&A) expenses: G&A expenses were $8.3 million for the three months ended June 30, 2024, compared to $8.2 million for the same period in 2023.

· Net loss: Net loss was $31.2 million for the three months ended June 30, 2024, compared to $33.3 million for the three months ended June 30, 2023.

Financial Guidance

· The Company expects full year generally accepted accounting principles (GAAP) operating expenses to be between $150 million and $160 million.

· The Company estimates its cash, cash equivalents, and investments will support operations into 2026.

On August 8, 2024 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, reported financial results for the second quarter ended June 30, 2024, and provided a business update (Press release, Cardiff Oncology, AUG 8, 2024, View Source [SID1234645588]).

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"The first half of 2024 has been productive for Cardiff Oncology as we have been focused on the enrollment of our CRDF-004 trial for first-line treatment of RAS-mutated mCRC evaluating onvansertib + chemo/bev," said Mark Erlander, Ph.D., Chief Executive Officer of Cardiff Oncology. "We are working closely with our clinical operations partner, Pfizer Ignite, and are encouraged by ongoing enrollment trends at the 33 sites currently open to enrollment. We believe the robust body of evidence generated to date from our Phase 1b/2 and ONSEMBLE trials lays a strong foundation for our upcoming data readout for CRDF-004 later this year. Furthermore, we are optimistic about the potential of onvansertib to change the treatment paradigm for the entire first-line RAS-mutated mCRC patient population who has not had access to any new therapies in over 20 years."

Upcoming expected milestones

•First-line RAS-mutated mCRC randomized data readout expected in 2H 2024
Company highlights for the quarter ended June 30, 2024 and subsequent weeks include:
•Updated clinical development plan for metastatic pancreatic ductal adenocarcinoma (mPDAC) with a planned new investigator-initiated trial
◦The new mPDAC trial will evaluate onvansertib in combination with the recently approved first-line standard of care, NALIRIFOX, details of which we will announce when available. The trial replaces a previously planned Phase 2 trial of onvansertib in combination with first-line standard of care, Gemzar and Abraxane.
•Published preclinical data of the combination of onvansertib and olaparib in olaparib-resistant ovarian cancer models in a peer-reviewed journal
◦The combination of onvansertib and olaparib, a PARP inhibitor approved in ovarian cancer, demonstrated inhibition of tumor growth and prolonged survival in olaparib-resistant high-grade serous ovarian carcinomas. The combination was well tolerated in vivo, and these findings underscore onvansertib’s ability to slow the progressions of ovarian carcinomas. Resistance to olaparib has been shown in clinical settings and these data support the ability of onvansertib to resensitize ovarian cancers to PARP inhibitors.
•Presented five abstracts at AACR (Free AACR Whitepaper) providing a strong scientific rationale for the clinical development of onvansertib across multiple tumor types and various combinations

◦The posters are located in the "Scientific Presentations" section of the Cardiff Oncology website and a press release summarizing the data can be found here.

Second Quarter 2024 Financial Results

Liquidity, cash burn, and cash runway
As of June 30, 2024, Cardiff Oncology had approximately $60.3 million in cash, cash equivalents, and short-term investments.
Net cash used in operating activities for the second quarter of 2024 was approximately $9.2 million, an increase of approximately $2.1 million from $7.1 million for the same period in 2023.
Based on its current expectations and projections, the Company believes its current cash resources are sufficient to fund its operations through the end of Q3 2025.
Operating results
Total operating expenses were approximately $12.7 million for the three months ended June 30, 2024, an increase of $0.4 million from $12.3 million for the same period in 2023. The increase in operating expenses was primarily due to clinical programs and outside service costs related to the development of our lead drug candidate, onvansertib, offset by an employee severance agreement which occurred during the previous period.

Conference Call and Webcast

Cardiff Oncology will host a corresponding conference call and live webcast at 4:30 p.m. ET/1:30 p.m. PT on August 8, 2024. Individuals interested in listening to the live conference call may do so by using the webcast link in the "Investors" section of the company’s website at www.cardiffoncology.com. A webcast replay will be available in the investor relations section on the company’s website following the completion of the call.

On August 8, 2024 Aura Biosciences, Inc. (NASDAQ: AURA), a clinical-stage biotechnology company developing precision therapies to treat a range of solid tumors designed to preserve organ function, reported financial results for the second quarter ended June 30, 2024, and provided recent business highlights (Press release, Aura Biosciences, AUG 8, 2024, View Source [SID1234645587]).

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"We are excited by the progress we made in the second quarter across all our clinical programs and in particular in our bladder cancer clinical trial. We look forward to our upcoming urologic oncology virtual event in October, where we plan to share early data in NMIBC," said Elisabet de los Pinos, Ph.D., Chief Executive Officer of Aura. "We are well-capitalized and remain focused on the execution of our ongoing clinical trials in ocular and urologic oncology, two areas where novel treatment options are needed that can provide effective local treatment while preserving organ function."

Recent Pipeline Developments

Bladder Cancer

A Phase 1 trial of bel-sar for the treatment of bladder cancer is currently ongoing. The company plans to host a virtual urologic oncology investor event featuring key opinion leaders (KOLs) in October 2024. Early NMIBC data from the ongoing Phase 1 trial is expected to be presented at this event.

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Bladder cancer represents an area of high unmet need with approximately 80,000 patients diagnosed in the United States annually. We believe bel-sar has the potential to selectively treat and induce a tumor specific immune response to prevent disease progression and recurrence, while allowing patients to be treated in-office by urologists and potentially avoiding the need for surgery. The Company received Fast Track designation from the FDA’s Division of Oncology for the treatment of NMIBC.

The ongoing Phase 1 multi-center, open-label clinical trial is expected to enroll approximately 21 adult patients. The trial is designed to assess the safety and feasibility of bel-sar as a monotherapy. The trial includes histopathological evaluation after local treatment to assess bel-sar’s biological activity, including the evaluation of focal necrosis and immune activation after a single dose of treatment.

Primary Uveal Melanoma

Phase 2 end of study data in small choroidal melanoma and indeterminate lesions will be presented at the Retina Society Annual Meeting taking place September 11-15, 2024, in Lisbon, Portugal.

Enrollment continues in global Phase 3 CoMpass trial for the treatment of small choroidal melanoma and indeterminate lesions.

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CoMpass trial continues to progress globally with site activations, patient enrollment and strong endorsement from the ocular oncology community. This trial has a global enrollment target of approximately 100 patients.

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CoMpass is a global, Phase 3, randomized, superiority trial evaluating bel-sar treatment against a sham control arm. Adult participants will be randomized 2:1:2 to undergo three cycles of treatment with either a high or low dose of bel-sar or to receive a sham control. The primary endpoint is time to tumor progression at 15 months of follow-up, as agreed upon with the United States Food and Drug Administration (FDA) under a Special Protocol Assessment (SPA).

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Early-stage choroidal melanoma represents an area of high unmet need with approximately 8,000 patients diagnosed in the United States and Europe annually. The Company received Orphan Drug Designation from the FDA and the European Medicines Agency (EMA) and Fast Track designation from the FDA for the treatment of primary uveal melanoma.

Additional Ocular Oncology Indications:

In addition to primary uveal melanoma, bel-sar is being explored for metastases to the choroid and cancers of the ocular surface. These three ocular oncology indications have a collective incidence of greater than 60,000 patients annually in the United States and Europe.

Metastases to the Choroid

The Company plans to initiate clinical development in metastases to the choroid, an indication with a high unmet medical need and no approved therapies. Metastases to the choroid is the second potential ocular oncology indication for bel-sar, affecting approximately 20,000 patients in the United States and Europe annually. The Company received Fast Track designation from the FDA’s Division of Oncology for the treatment of metastases to the choroid. The Company is on track to initiate a Phase 2 trial in 2024.

Cancers of the Ocular Surface

Cancers of the ocular surface is the Company’s third potential ocular oncology indication affecting approximately 35,000 patients in the United States and Europe annually. The Company continues to advance its preclinical work designed to be IND-enabling in cancers of the ocular surface.

Recent Corporate Events

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The Company hosted a virtual KOL event with global opinion leaders in Ocular Oncology, "Pioneering a New Standard of Care in Ocular Oncology," on May 29, 2024. A replay of the webcast is available on the "Investors & Media" page under the "Events & Presentations" section of Aura’s website at View Source

Second Quarter 2024 Financial Results

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As of June 30, 2024, Aura had cash and cash equivalents and marketable securities totaling $187.4 million. The Company believes its current cash and cash equivalents and marketable securities are sufficient to fund its operations into the second half of 2026.

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Research and development expenses increased to $16.9 million for the three months ended June 30, 2024 from $15.1 million for the three months ended June 30, 2023, primarily due to higher personnel expenses related to growth of our Company.

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General and administrative expenses increased to $5.9 million for the three months ended June 30, 2024 from $5.2 million for the three months ended June 30, 2023. General and administrative expenses include $1.6 million and $1.2 million of stock-based compensation for the three months ended June 30, 2024 and 2023, respectively. The increase was primarily driven by personnel expenses, as well as increases in general corporate expenses related to the growth of our Company.

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Net loss for the three months ended June 30, 2024 was $20.3 million compared to $18.3 million for the three months ended June 30, 2023.

On August 8, 2024 Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for people with cancer, reported financial results for the second quarter ended June 30, 2024, and provided a pipeline update on its clinical-stage investigational molecules – targeting TIGIT, the adenosine axis (CD73 and A2a/A2b receptors), HIF-2a, AXL and PD-1 – across multiple common cancers (Press release, Arcus Biosciences, AUG 8, 2024, View Source [SID1234645586]).

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"Our upcoming presentation of efficacy and safety data for casdatifan will demonstrate that it has the potential to be the best-in-class HIF-2a inhibitor," said Terry Rosen, Ph.D., chief executive officer of Arcus. "We are pursuing a broad development program in both first- and second-line settings, as well as differentiated combinations, to maximize the opportunity for casdatifan in ccRCC. Meanwhile, the accumulating data continue to enhance our confidence that our Fc-silent anti-TIGIT antibody, domvanalimab, has the potential for an improved safety profile over that of Fc-enabled antibodies, particularly when combined with chemotherapy, which may also result in an efficacy advantage for domvanalimab. With STAR-221 enrollment completed, we are looking forward to our first Phase 3 data readout."
Corporate Updates:
•In July 2024, Taiho Pharmaceutical (Taiho) exercised its option for quemliclustat, an investigational small molecule CD73 inhibitor, in Japan and certain other territories in Asia (excluding mainland China). As a result of this option exercise, Taiho will operationalize the Phase 3 PRISM-1 study evaluating quemliclustat in pancreatic cancer in Japan, and Arcus will receive an opt-in payment and is eligible to receive near-term milestone payments.
Pipeline Highlights:
Casdatifan (HIF-2a inhibitor)
•Multiple expansion cohorts evaluating casdatifan in clear cell renal cell carcinoma (ccRCC) are underway, with several data presentations expected in the next 18 months. Each cohort is enrolling approximately 30 patients.
◦ARC-20: Phase 1/1b study evaluating casdatifan as a monotherapy and in combination with other agents:
▪100 mg daily expansion cohort in 2L+ ccRCC: ORR data are expected to be presented in the fourth quarter of 2024.
▪50 mg and 150 mg expansion cohorts in 2L+ ccRCC: Enrollment has been completed for both cohorts and data are expected to be presented in 2025.
▪An expansion cohort evaluating casdatifan in combination with cabozantinib in 2L+ ccRCC is also enrolling.
•Following FDA feedback later this year, Arcus plans to initiate its first Phase 3 study, PEAK-1, evaluating casdatifan in combination with cabozantinib versus cabozantinib monotherapy in patients with metastatic ccRCC who have previously received anti-PD-1 therapy, in the first half of 2025.

•Arcus is in advanced stages of planning with a clinical collaboration partner to evaluate casdatifan in a potential first-in-class combination regimen for first-line metastatic ccRCC.
Domvanalimab (Fc-silent anti-TIGIT antibody) plus Zimberelimab (anti-PD-1 antibody)
Domvanalimab-Zimberelimab Updates:
•Updated data presented at the ASCO (Free ASCO Whitepaper) Annual Meeting from Arm A1 of the Phase 2 EDGE-Gastric study showed 12.9 months median progression-free survival (PFS) for domvanalimab plus zimberelimab and chemotherapy in first-line upper GI adenocarcinomas, which exceeded historical benchmarks for anti-PD-1 plus chemotherapy.
◦The EDGE-Gastric study is evaluating the same regimen in the same setting as the STAR-221 Phase 3 study.
•STAR-221, a Phase 3 study evaluating domvanalimab plus zimberelimab and chemotherapy in PD-L1 all-comer first-line metastatic upper GI adenocarcinomas, completed enrollment in June.
•STAR-121, a Phase 3 study evaluating domvanalimab plus zimberelimab and chemotherapy in PD-L1 all-comer first-line metastatic non-small cell lung cancer (NSCLC), is expected to complete enrollment in 2024.
Upcoming Domvanalimab-Zimberelimab Milestones:
•Overall survival (OS) and PFS data from previously enrolled patients in Part 1 of the Phase 3 ARC-10 study, evaluating domvanalimab plus zimberelimab versus zimberelimab versus chemotherapy in first-line PD-L1-high NSCLC, are expected to be presented by the end of 2024.
•OS data from the Phase 2 EDGE-Gastric study, evaluating domvanalimab plus zimberelimab and chemotherapy in upper GI adenocarcinomas, are expected to be presented in 2025.
CD73-Adenosine Axis: Etrumadenant (A2a/A2b receptor antagonist) and Quemliclustat (small-molecule CD73 inhibitor)
Etrumadenant
•Cohort B data from ARC-9, a randomized Phase 1b/2 study evaluating etrumadenant plus zimberelimab, FOLFOX chemotherapy and bevacizumab (EZFB) versus regorafenib in third-line metastatic colorectal cancer (mCRC), were presented at ASCO (Free ASCO Whitepaper) in June.
◦Results showed 19.7 months median OS for the EZFB arm, and EZFB significantly reduced the risk of death by 63% and risk of disease progression by 73% compared to regorafenib. This is the longest median OS reported in third-line mCRC to date in a randomized trial.
◦Biomarker data from this study are expected to be presented at a scientific conference in the second half of 2024.
•Based on these encouraging results, Arcus and Gilead are determining next steps for the development of etrumadenant in mCRC.
Quemliclustat
•Initiation of a Phase 3 trial, PRISM-1, of quemliclustat combined with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel in pancreatic cancer is expected to begin by early 2025.
•Taiho exercised its option for an exclusive license to quemliclustat in Japan and certain territories in Asia and will operationalize PRISM-1 in Japan.
Early Clinical Programs
•Dose escalation for AB801, a potent and highly selective small-molecule AXL inhibitor, continues. Arcus anticipates advancing this molecule into expansion cohorts in NSCLC in early 2025.
Financial Results for Second Quarter 2024:
•Cash, Cash Equivalents and Marketable Securities were $1.0 billion as of June 30, 2024, compared to $866 million as of December 31, 2023. The increase during the period is primarily due to the receipt of $320 million in cash from Gilead for their January 2024 equity investment, partially offset by the use of cash in research and development activities. We believe our cash, cash equivalents and marketable securities on-hand will be sufficient to fund operations into 2027. Cash, cash equivalents and marketable securities are expected to be between $885 million and $925 million at the end of 2024.

•Revenues were $39 million for the second quarter 2024, compared to $29 million for the same period in 2023. In the second quarter 2024, Arcus recognized $28 million in license and development services revenue related to the advancement of programs, as well as $11 million in other collaboration revenue primarily related to Gilead’s ongoing rights to access Arcus’s research and development pipeline in accordance with the Gilead collaboration agreement.
•Research and Development (R&D) Expenses were $115 million for the second quarter 2024, compared to $84 million for the same period in 2023. The net increase of $31 million was primarily driven by higher clinical trial and headcount-related costs associated with our late-stage development program activities. Non-cash stock-based compensation expense was $10 million for the second quarter 2024, compared to $9 million for the same period in 2023. For the second quarter 2024 and 2023, Arcus recognized gross reimbursements of $40 million and $44 million, respectively, for shared expenses from its collaborations, primarily the Gilead collaboration. R&D expense by quarter may fluctuate due to the timing of clinical manufacturing and standard-of-care therapeutic purchases with a corresponding impact on reimbursements.
•General and Administrative (G&A) Expenses were $30 million for the second quarter 2024, compared to $28 million for the same period in 2023. The increase was primarily driven by higher headcount and costs incurred to obtain the Third Gilead Agreement Amendment. Non-cash stock-based compensation expense was $10 million for the second quarter 2024, compared to $9 million for the same period in 2023.
•Net Loss was $93 million for the second quarter 2024, compared to $75 million for the same period in 2023.

Conference Call Information:
Arcus will host a conference call and webcast today, August 8, at 2:00 PM PT / 5:00 PM ET to discuss its second-quarter 2024 financial results and pipeline updates. To access the call, please dial (404) 975-4839 (local) or (833) 470-1428 (toll-free), using Access Code: 287576. To access the live webcast and accompanying slide presentation, please visit the "Investors & Media" section of the Arcus Biosciences website at www.arcusbio.com. A replay of the webcast will be available following the live event.

Arcus Ongoing and Announced Clinical Studies:
Trial Name Arms Setting Status NCT No.
Lung Cancer
STAR-121
dom + zim + chemo vs. pembro + chemo 1L NSCLC (PD-L1 all-comers) Ongoing Registrational Phase 3 NCT05502237
PACIFIC-8
dom + durva vs. durva Unresectable Stage 3 NSCLC Ongoing Registrational Phase 3 NCT05211895
STAR-131 dom + zim + chemo; dom + zim Perioperative NSCLC Registrational Phase 3 In Planning TBD
ARC-7 zim vs. dom + zim vs. etruma + dom + zim 1L NSCLC (PD-L1 ≥ 50%) Ongoing Randomized Phase 2 NCT04262856
EDGE-Lung dom +/- zim +/- quemli +/- chemo 1L/2L NSCLC (lung cancer platform study) Ongoing Randomized Phase 2 NCT05676931
VELOCITY-Lung
dom +/- zim +/- etruma +/- sacituzumab govitecan-hziy or other combos 1L/2L NSCLC (lung cancer platform study) Ongoing Randomized Phase 2 NCT05633667
Upper Gastrointestinal Cancers
STAR-221 dom + zim + chemo vs. nivo + chemo 1L Gastric, GEJ and EAC Ongoing Registrational Phase 3 NCT05568095
EDGE-Gastric (ARC-21) dom +/- zim +/- quemli +/- chemo 1L/2L Upper GI Malignancies
Ongoing
Randomized Phase 2
NCT05329766
Colorectal Cancer
ARC-9 etruma + zim + mFOLFOX vs. SOC 2L/3L/3L+ CRC Ongoing
Randomized Phase 2
NCT04660812
Pancreatic Cancer
PRISM-1 quemli + gem/nab-pac vs. gem/nab-pac 1L PDAC Planned Phase 3 TBD
ARC-8 quemli + zim + gem/nab-pac vs. quemli + gem/nab-pac 1L, 2L PDAC Ongoing Randomized Phase 1/1b NCT04104672
Kidney Cancer
PEAK-1 cas + cabo vs. cabo Post-IO ccRCC Planned Phase 3 TBD
STELLAR-009 cas + zanza ccRCC Ongoing Phase 1b/2 NCT06191796
ARC-20 cas, cas + cabo Cancer Patients / ccRCC Ongoing Phase 1/1b NCT05536141
Other
ARC-25 AB598 Advanced Malignancies Ongoing NCT05891171
ARC-27 AB801 Advanced Malignancies Ongoing NCT06120075

cabo: cabozantinib; cas: casdatifan; dom: domvanalimab; durva: durvalumab; etruma: etrumadenant; gem/nab-pac: gemcitabine/nab-paclitaxel; nivo: nivolumab; pembro: pembrolizumab; quemli: quemliclustat; SOC: standard of care; zanza: zanzalintinib; zim: zimberelimab; ccRCC: clear cell renal cell carcinoma; CRC: colorectal cancer; EAC: esophageal adenocarcinoma; GEJ: gastroesophageal junction; GI: gastrointestinal; NSCLC: non-small cell lung cancer; PDAC: pancreatic ductal adenocarcinoma