On April 26, 2024 Citius Pharmaceuticals Inc. (Nasdaq: CTXR) ("Citius" or the "Company"), a late-stage biopharmaceutical company dedicated to the development and commercialization of first-in-class critical care products, reported that it has entered into definitive agreements for the purchase of an aggregate of 21,428,574 shares of its common stock and accompanying warrants to purchase up to an aggregate of 21,428,574 shares of its common stock, at a purchase price of $0.70 per share and accompanying warrant in a registered direct offering (Press release, Citius Pharmaceuticals, APR 26, 2024, View Source [SID1234642398]). The warrants will have an exercise price of $0.75 per share, will be exercisable six months from the date of issuance, and will expire five years from the initial exercise date. The closing of the offering is expected to occur on or about April 30, 2024, subject to the satisfaction of customary closing conditions.

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H.C. Wainwright & Co. is acting as the exclusive placement agent for the offering.

The aggregate gross proceeds to the Company from the offering are expected to be approximately $15 million, before deducting the placement agent fees and other offering expenses payable by the Company. Citius currently intends to use the net proceeds from the offering for general corporate purposes, including pre-clinical and clinical development of our product candidates and working capital and capital expenditures.

The securities described above are being offered pursuant to a "shelf" registration statement (File No. 333-277319) filed with the Securities and Exchange Commission ("SEC") on February 23, 2024 and declared effective on March 1, 2024. The offering is being made only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. The prospectus supplement and the accompanying prospectus relating to the securities being offered will be filed with the SEC and be available at the SEC’s website at www.sec.gov. Electronic copies of the prospectus supplement and the accompanying prospectus relating to the securities being offered may also be obtained, when available, by contacting H.C. Wainwright & Co., LLC at 430 Park Avenue, 3rd Floor, New York, NY 10022, by telephone at (212) 856-5711 or e-mail at [email protected].

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

On April 26, 2024 Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) products for cancer and autoimmune disease, reported that it has received a $15 million grant from the California Institute for Regenerative Medicine (CIRM) to support the clinical development of ALLO-316, an AlloCAR T investigational product targeting CD70 in development for the treatment of advanced or metastatic renal cell carcinoma (RCC) (Press release, Allogene, APR 26, 2024, View Source [SID1234642396]).

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"CAR T has transformed the treatment of hematologic malignancies but there remains a significant opportunity to apply this innovation to solid tumors," said Zachary Roberts, M.D., Ph.D., Executive Vice President, Research & Development and Chief Medical Officer of Allogene. "We believe this CIRM award validates the remarkable inroads we have made in our TRAVERSE trial to date and the therapeutic potential ALLO-316 has for patients with advanced RCC who have failed standard therapies. We look forward to advancing this trial with the added support of this grant and are grateful for the recognition from the CIRM reviewers of the potential for ALLO-316 to make a difference for patients."

Metastatic RCC is the most common kidney cancer globally and there are limited options for treatment after treatments with checkpoint blockers and targeted therapy have failed. It is a disease in need of innovation as current therapies are based on a few mechanistic targets and complete response rates are low. The five-year survival rate for patients with advanced kidney cancer is less than 17%1.

The grant will support the ongoing Phase 1 TRAVERSE trial which assesses safety, tolerability and preliminary efficacy of ALLO-316 in advanced RCC that has progressed despite standard therapy. Initial data from the TRAVERSE trial, presented at AACR (Free AACR Whitepaper) 2023, showed promising response rates and early anti-tumor activity with deepening responses over time in participants with a marked unmet medical need. In the TRAVERSE trial, ALLO-316 has demonstrated the potency of the Dagger technology, which selectively eliminates CD70 positive, alloreactive host immune cells, thus delaying or preventing premature rejection of AlloCAR T cells by the patient’s immune system. ALLO-316 has shown marked expansion and persistence both in preclinical experiments and in clinical trial patients, even when combined with comparatively less-intense lymphodepletion regimens. The intent of this grant will be to facilitate completion of the Phase 1 portion of the trial, including expansion of clinical sites to increase access for diverse patient populations. Additionally, the grant will support translational and clinical analyses to inform a recommended Phase 2 regimen.

"This clinical study has the potential to demonstrate the value of Chimeric Antigen Receptor (CAR) T cell therapy in solid cancers such as kidney cancer with a high unmet medical need," said Dr. Abla Creasey, PhD, Vice President of Therapeutics Development at CIRM.

Details on a potentially cornerstone safety algorithm discovered during the initial portion of the Phase 1 TRAVERSE trial, which may facilitate expanded use of CAR Ts in solid tumors, is planned for a publication in Q2 2024. A more comprehensive data update from the ongoing trial is planned for later in 2024.

About ALLO-316 (TRAVERSE)
ALLO-316, an AlloCAR T investigational product targets CD70, which is highly expressed in renal cell carcinoma (RCC). CD70 is also selectively expressed in several cancers, creating the potential for ALLO-316 to be developed across a variety of both hematologic malignancies and solid tumors. The ongoing Phase 1 TRAVERSE trial is designed to evaluate the safety, tolerability, and activity of ALLO-316 in patients with advanced or metastatic clear cell RCC. In March 2022, the U.S. Food and Drug Administration granted Fast Track Designation (FTD) based on the potential of ALLO-316 to address the unmet need for patients with difficult to treat RCC who have failed standard RCC therapies.

On April 26, 2024 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:​HCM; HKEX:​13) reported that its partner Takeda (TSE:​4502/​NYSE:​TAK) received notification that the Committee for Medicinal Products for Human Use ("CHMP") of the European Medicines Agency ("EMA") has recommended the approval of fruquintinib for the treatment of adult patients with previously treated metastatic colorectal cancer ("CRC") (Press release, Hutchison China MediTech, APR 26, 2024, View Source [SID1234642391]).

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The European Commission (EC) will consider the CHMP positive opinion when determining the potential marketing authorization for fruquintinib for metastatic CRC throughout the European Union ("EU"), Norway, Liechtenstein and Iceland. If approved, fruquintinib will be the first and only selective inhibitor of all three vascular endothelial growth factor receptors ("VEGFR") approved in the EU for previously treated metastatic CRC. [1],[2] Takeda has the exclusive worldwide license to further develop, commercialize, and manufacture fruquintinib outside of mainland China, Hong Kong and Macau.

"Through our partnership with HUTCHMED, we have made strides in expanding access to fruquintinib to eligible patients. With this positive CHMP opinion for fruquintinib, we are one step closer to potentially offering patients in the EU an oral, chemotherapy‑free option that can provide a significant survival benefit," said Awny Farajallah, M.D., Chief Medical Officer, Oncology at Takeda. "We look forward to the European Commission’s official decision in the near future."

"HUTCHMED has a strong track record of developing innovative oncology medicines for patients in need. People living with metastatic CRC in the EU currently have limited treatment options available to them, which can lead to poor outcomes. We are pleased with our partner Takeda’s progress toward redefining the treatment landscape and helping to address a significant unmet need for those affected by metastatic CRC in Europe," said Weiguo Su, PhD, Chief Executive Officer and Chief Scientific Officer of HUTCHMED. "This novel oncology medicine has had a profound impact for patients in China over the last five years. Since entering our partnership with Takeda we have seen this impact extended with its approval and launch in the U.S. and, pending approval by the European Commission, we look forward to the medicine having a positive effect for patients in Europe too."

The CHMP’s positive opinion was primarily based on results from the Phase III multi‑regional FRESCO‑2 trial, which supported the Marketing Authorisation Application ("MAA"). The MAA was validated and accepted for review by the EMA in June 2023.

About CRC
CRC is a cancer that starts in either the colon or rectum. According to the International Agency for Research on Cancer, CRC is the third most prevalent cancer worldwide, associated with more than 935,000 deaths in 2020. In Europe, CRC was the second most common cancer in 2020, with approximately 520,000 new cases and 245,000 deaths.[3] In the U.S., it is estimated that 153,000 patients will be diagnosed with CRC and 53,000 deaths from the disease will occur in 2024.[4] In Japan, CRC was the most common cancer, with an estimated 148,000 new cases and 60,000 deaths, in 2020.3 Although early‑stage CRC can be surgically resected, metastatic CRC remains an area of high unmet need with poor outcomes and limited treatment options. Some patients with metastatic CRC may benefit from personalized therapeutic strategies based on molecular characteristics; however, most patients have tumors that do not harbor actionable mutations.[5],[6],[7],[8],[9]

About the Phase III FRESCO‑2 Trial
FRESCO‑2 is a multi‑regional clinical trial conducted in the U.S., Europe, Japan and Australia investigating fruquintinib plus best supportive care ("BSC") versus placebo plus BSC in patients with previously treated mCRC (NCT04322539). FRESCO-2 met all of its primary and key secondary endpoints, demonstrating statistically significant and clinically meaningful improvement in overall survival (OS) and progression-free survival (PFS), with consistent benefit among patients treated with fruquintinib, regardless of the prior types of therapies they received. Fruquintinib demonstrated a manageable safety profile in FRESCO‑2, consistent with previously reported fruquintinib studies. Adverse reactions leading to treatment discontinuation occurred in 20% of patients treated with fruquintinib plus BSC versus 21% of those treated with placebo plus BSC. Results from the study were presented at the European Society for Medical Oncology Congress (ESMO) (Free ESMO Whitepaper) in September 2022 and subsequently published in The Lancet in June 2023.[10],[11]

About Fruquintinib
Fruquintinib is a selective oral inhibitor of VEGFR‑1, ‑2 and ‑3. VEGFR inhibitors play a pivotal role in inhibiting tumor angiogenesis. Fruquintinib was designed to have enhanced selectivity that limits off‑target kinase activity, allowing for high drug exposure, sustained target inhibition, and flexibility for its potential use as part of a combination therapy. Fruquintinib has demonstrated a manageable safety profile and is being investigated in combinations with other anti‑cancer therapies.

On April 26, 2024 Bristol Myers Squibb (NYSE: BMY) reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended approval of Opdivo (nivolumab) in combination with cisplatin and gemcitabine for the first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma (Press release, Bristol-Myers Squibb, APR 26, 2024, View Source [SID1234642390]). The European Commission (EC), which has the authority to approve medicines for the European Union (EU), will now review the CHMP recommendation. The final EC decision is expected in June 2024.

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"For eligible patients with unresectable or metastatic urothelial carcinoma, platinum-based chemotherapy in the first-line setting has been the standard of care for decades but the durability of response to chemotherapy alone is poor and once a patient progresses, treatment options become increasingly limited," said Dana Walker, vice president and Global Program Lead, Genitourinary Cancers, Bristol Myers Squibb. "New treatment options that may improve responses, delay disease progression, and offer survival benefit in the first-line setting are needed. With today’s CHMP positive opinion, we are one step closer to potentially providing eligible patients with unresectable or metastatic urothelial carcinoma in the European Union with a new first-line treatment option."

The positive CHMP opinion is based on results from a sub-study of the CheckMate -901 trial which were presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023. In the sub-study, Opdivo in combination with cisplatin and gemcitabine followed by Opdivo monotherapy demonstrated statistically significant and clinically meaningful improvements in the primary efficacy endpoints of overall survival (OS) and progression-free survival (PFS) as assessed by Blinded Independent Central Review (BICR). With a median follow up of approximately 33 months, treatment with Opdivo in combination with cisplatin and gemcitabine reduced the risk of death by 22%, demonstrating a median OS of 21.7 months versus 18.9 months with cisplatin-gemcitabine alone (Hazard Ratio [HR] 0.78; 95% Confidence Interval [CI]: 0.63, 0.96; p=0.0171). Patients receiving Opdivo in combination with cisplatin and gemcitabine had their risk of disease progression or death reduced by 28%, with a median PFS of 7.9 months compared to 7.6 months with cisplatin-gemcitabine alone (HR 0.72; 95% CI: 0.59, 0.88; p=0.0012). The safety profile was consistent with the known safety profiles of the individual components of the regimen. No new safety concerns were identified. Please see Important Safety Information below.

CheckMate -901 is the first Phase 3 trial with an immunotherapy-chemotherapy combination to demonstrate a survival benefit compared to standard-of-care chemotherapy alone in the first-line treatment of adults with unresectable or metastatic urothelial carcinoma.

On March 7, 2024 the U.S. Food and Drug Administration (FDA) approved the use of Opdivo in combination with cisplatin and gemcitabine as a first-line treatment for adult patients with unresectable or metastatic urothelial carcinoma, following a Priority Review. Opdivo and Opdivo-based combinations have shown significant improvements in OS in Phase 3 clinical trials across multiple tumors, including urothelial carcinoma, renal cell carcinoma, non-small cell lung cancer, malignant pleural mesothelioma, melanoma, hepatocellular carcinoma, gastric cancer, squamous cell carcinoma of the head and neck and esophageal squamous cell carcinoma.

Bristol Myers Squibb thanks the patients and investigators involved in the CheckMate -901 clinical trial.

About CheckMate -901

CheckMate -901 is a Phase 3, randomized, open-label trial evaluating Opdivo in combination with Yervoy (ipilimumab) or Opdivo in combination with cisplatin and gemcitabine followed by Opdivo monotherapy compared to standard-of-care chemotherapy alone, in patients with untreated, unresectable or metastatic urothelial cancer.

In the sub-study of CheckMate -901, evaluating Opdivo with cisplatin and gemcitabine vs. standard-of-care chemotherapy alone, a total of 608 patients eligible for cisplatin-based chemotherapy were randomized to receive either Opdivo 360 mg in combination with cisplatin and gemcitabine every three weeks for up to six cycles followed by 480 mg/Q4 Opdivo monotherapy every 4 weeks until disease progression or death up to a maximum of two years, or cisplatin-gemcitabine alone every three weeks for up to six cycles. The primary endpoints of this study are overall survival (OS) and progression-free survival (PFS).

The OS and PFS outcomes for patients eligible for cisplatin-based chemotherapy are based on the final efficacy analyses of these endpoints.

The CheckMate -901 primary study, evaluating Opdivo plus Yervoy vs. standard-of-care cisplatin- or carboplatin-based chemotherapy in patients with untreated, unresectable or metastatic urothelial carcinoma remains ongoing.

About Urothelial Carcinoma

Bladder cancer is the 10th most common cancer in the world, with more than 573,000 new cases diagnosed annually. Urothelial carcinoma, which most frequently begins in the cells that line the inside of the bladder, accounts for approximately 90% of bladder cancer cases. In addition to the bladder, urothelial carcinoma can occur in other parts of the urinary tract, including the ureters and renal pelvis. The majority of urothelial carcinomas are diagnosed at an early stage, but approximately 50% of patients who undergo surgery will experience disease progression and recurrence within two-to-three years post-surgery. Approximately 20% to 25% of patients with urothelial carcinoma develop metastatic disease. The poor durability of responses seen with chemotherapy alone in the first-line setting presents a major challenge in the treatment of metastatic disease, and there are limited treatment options in the second-line setting for patients with advanced urothelial carcinoma.

On April 26, 2024, BeiGene, Ltd. (the "Company") filed its 2023 Annual Report (the "STAR Annual Report") with the Science and Technology Innovation Board (the "STAR Market") of the Shanghai Stock Exchange, which was prepared in accordance with the listing rules of the STAR Market and the applicable securities laws and regulations of the Peoples’ Republic of China (the "PRC" and the "PRC Securities Laws") (Press release, BeiGene, APR 26, 2024, View Source [SID1234642389]). The STAR Annual Report is available to the public in Chinese language only on the website maintained by the Shanghai Stock Exchange at www.sse.com.cn.

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As required by the PRC Securities Laws, the STAR Annual Report contains additional financial information of the Company’s gross profit margin ratio, research and development expenses allocated by key products and other research and development projects and production, sales and inventory stock units for the year ended December 31, 2023 (the "Reporting Period"), prepared in accordance with the China Accounting Standards for Business Enterprises – Basic Standard ("CAS") and other applicable PRC accounting rules, guidance and interpretations (together with CAS, "PRC GAAP"), including but not limited to the China Securities Regulatory Commission’s Compilation Rule for Information Disclosure by Companies Offering Securities to the Public No. 15 – General Rules for Financial Statement (2023 revised), and Compilation Rule for Information Disclosure by Companies Offering Securities to the Public No. 24-Special Provisions on Information Disclosure in Financial Statements of Pilot Innovative Red-chip Companies on the Sci-Tech Innovation Board. The key differences between such financial information prepared in accordance with PRC GAAP and those prepared in accordance with accounting principles generally accepted in the United States ("U.S. GAAP") for the Reporting Period, which was previously filed with the U.S. Securities and Exchange Commission, are summarized below.

Key Differences between PRC GAAP and U.S. GAAP

Share-based Compensation

Under U.S. GAAP, the Company elects to recognize share-based compensation expenses using the straight-line method for all employee equity awards granted with graded vesting based on service conditions, provided that the amount of compensation cost recognized at any date is at least equal to the portion of the grant-date value of the options that are vested as of that date.

Under PRC GAAP, the Company recognizes share-based compensation expense using the accelerated method for all employee equity awards granted with graded vesting.

Under PRC GAAP, the excess tax benefit resulting from the pre-tax deductible amount arising from U.S. employee share-based payments over the cumulative share-based payment-related expenses recognized for accounting purposes should be recorded in shareholders’ equity rather than in current income tax expenses/benefits under U.S. GAAP.

Leasing

Under U.S. GAAP, as a lessee, the Company recognizes a lease liability based on the present value of the total remaining lease payments, and a corresponding right-of-use assets. The Company subsequently recognizes operating lease expenses on a straight-line basis over the lease term.

PRC GAAP requires lessees to present interest expenses on the lease liability and depreciation on the right-of-use assets separately in the statements of operations. The combination of a straight-line depreciation of the right-of-use assets and the effective interest rate method applied to the lease liability will result in a higher total charge to profit or loss in the initial years of the leases and decreasing expenses during the latter part of the lease term.

Gross Profit Margin Ratio

As required by the PRC Securities Laws, the 2023 STAR Annual Report contained financial information regarding gross profit margin ratio by region, which was prepared in accordance with PRC GAAP. The corresponding financial information prepared in accordance with U.S. GAAP is presented below. Amounts reported herein are stated in thousands of U.S. dollars.
For the year ended December 31, 2023
For the year ended December 31, 2022
By Region
Revenue
COGS
Gross Margin ratio
Revenue
COGS
Gross Margin ratio
China
1,101,951
352,706
68.0%
840,032
276,729
67.1%
Ex-China
1,356,828
27,214
98.0%
575,889
9,746
98.3%
Total
2,458,779
379,920
–
1,415,921
286,475

Research and Development Expenses Allocated by Key Products and Other R&D Projects

As required by the PRC Securities Laws, the 2023 STAR Annual Report contains financial information regarding the research and development ("R&D") expenses allocated by key products, which was prepared in accordance with PRC GAAP. The corresponding financial information prepared in accordance with U.S. GAAP is presented below. Amounts reported herein are stated in thousands of U.S. dollars.
Pipeline Products/ Projects
For the year ended December 31, 2023
For the year ended December 31, 2022
Zanubrutinib
158,051
126,959
Tislelizumab
83,799
88,935
Pamiparib
8,963
11,606
Ociperlimab (BGB-A1217)
77,717
106,608
Bcl-2 (BGB-11417)
52,548
22,377
OX40 (BGB-A445)
15,757
11,215
CDAC (BGB-16673)
3,584
1,071
Other R&D projects
150,998
100,726
R&D collaboration projects
100,115
167,620
Subtotal of external R&D expenses
651,532
637,117
Subtotal of internal R&D expenses
1,127,062
1,003,391
Total
1,778,594
1,640,508

Production, Sales and Inventory Stock Units

As required by the PRC Securities Laws, the 2023 STAR Annual Report contained financial information regarding the production, sales and inventory stock units of key products, which was prepared in accordance with PRC GAAP. The corresponding financial information prepared in accordance with U.S. GAAP is presented below.

Item
Unit
Production or purchase quantity for the year ended December 31, 2023
Sales quantity for the year ended December 31, 2023
Stock quantity as of December 31, 2023
Key products
vials
5,004,600
3,878,000
2,666,400