On February 21, 2024 Curium, a world leader in nuclear medicine, reported that the marketing authorization application for PYLCLARI (INN: Piflufolastat (18F) formerly known as (18F)-DCFPyL) submitted by exclusive Swiss distributor b.e.imaging AG on 31 January 2024 to the Swiss Agency for Therapeutic Products (Swissmedic) has been accepted for evaluation (Press release, Curium, FEB 21, 2024, View Source [SID1234640322]).

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PYLCLARI is indicated for the detection of prostate-specific membrane antigen (PSMA) positive lesions with positron emission tomography (PET) in adults with prostate cancer (PCa) in the following clinical settings:

Primary staging of patients with high-risk PCa prior to initial curative therapy
To localize recurrence of PCa in patients with a suspected recurrence based on increasing serum prostate-specific antigen (PSA) levels after primary treatment with curative intent
Prostate cancer is one of the most frequently diagnosed cancers in men in Europe, accounting for around 23 percent of all new cancer cases in 2020 and nearly 10 percent of all deaths due to cancer in men.

Dr. Michel Wuillemin, Head of Radiopharmaceuticals at b.e. imaging commented, "b.e.Imaging is proud of the submission of the marketing authorization application for PYLCLARI to Swissmedic ahead of schedule. We are fully dedicated to improving the situation of prostate cancer patients in Switzerland."

Benoit Woessmer, PET Europe CEO at Curium commented, "The acceptance of the marketing authorization application by Swissmedic for PYLCLARI is another important milestone for prostate cancer patients in Switzerland. We look forward to providing an improved choice of tools available to physicians for the diagnosis of prostate cancer patients. Importantly, when in full production PYLCLARI is expected to be the most widely available 18F-PSMA tracer in Europe."

The submission to Swissmedic by b.e.imaging AG was based on Curium’s Marketing Authorization Application for (18F)-DCFPyL submitted to the European Medicines Agency in July 2022. Marketing authorization for PYLCLARI (also known as (18F)-DCFPyL) was granted in July 2023 by the European Commission.

b.e.imaging AG currently distributes Curium’s entire suite of SPECT imaging products across Switzerland and has exclusive distribution rights for PYLCLARI in Switzerland. When authorization is received, PYLCLARI will be supplied by three of Curium’s European facilities.

For more information about PYLCLARI: View Source

In the U.S., Lantheus received approval for [18F]-DCFPyL, now PYLARIFY (Piflufolastat F 18 Injection) from the Food and Drug Administration (FDA) in May 2021. It is the #1 PSMA PET Imaging Agent in the U.S. market. The European rights were licensed by Curium from Progenics, a Lantheus company, in 2018.

On February 21, 2024 CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, reported financial results for the fourth quarter and full year ended December 31, 2023 (Press release, CRISPR Therapeutics, FEB 21, 2024, View Source [SID1234640321]).

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"2023 was a monumental year for CRISPR Therapeutics, with multiple milestones achieved across our pipeline, including the first-ever approval of a CRISPR-based gene-editing therapy in addition to entering the clinic with our first in vivo programs targeting cardiovascular diseases," said Samarth Kulkarni, Ph.D., Chairman and Chief Executive Officer of CRISPR Therapeutics. "We continue to advance our next generation CAR T cell programs, CTX112 and CTX131, which have the potential to be best-in-class cell therapies for the treatment of both liquid and solid tumors. Additionally, we plan to initiate a clinical trial of CTX112 in systemic lupus erythematosus (SLE) in the first half of 2024, with the potential to expand into additional autoimmune indications in the future. We are excited about our first two in vivo programs that are now in the clinic, and also expect to nominate additional in vivo programs targeting both rare and common diseases mid-year. I am incredibly excited about the year ahead as we continue to innovate across our platform and execute on our clinical trials across various therapeutic areas, including oncology, autoimmune, cardiovascular and diabetes, setting up a catalyst-rich 12-18 months for the company."

Recent Highlights and Outlook

Hemoglobinopathies and CASGEVY (exagamglogene autotemcel [exa-cel])
CASGEVY has been approved in the U.S., E.U., Great Britain, Bahrain, and the Kingdom of Saudi Arabia (KSA) for the treatment of patients with either sickle cell disease (SCD) or transfusion-dependent beta thalassemia (TDT). Nearly 35,000 patients are living with severe SCD or TDT in the U.S. and Europe alone. 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.
The regulatory submission for CASGEVY for both SCD and TDT is currently under review in Switzerland, with submission in Canada planned for the first half of 2024.
Vertex reported progress on CASGEVY launch in the U.S. with the activation of 12 authorized treatment centers (ATCs) in the U.S. and the signing of an agreement with Synergie Medication Collective, a contracting organization which supports payors covering approximately 100 million people in the U.S., to provide access to CASGEVY. Additionally, Vertex is actively engaging with state Medicaid organizations to secure immediate reimbursement and coverage for CASGEVY.
Outside the U.S., Vertex reported progress on the launch with the activation of three authorized treatment centers in the E.U. and one in KSA. Additionally, the French National Authority for Health (HAS) approved a request for the implementation of an early access program (EAP) for the use of CASGEVY to treat eligible people with TDT. Vertex is also pursuing an EAP submission for SCD in France and expects to hear the outcome of this decision in the coming months.
CRISPR Therapeutics has two next-generation approaches that each have the potential to expand the addressable population with SCD and TDT significantly. CRISPR Therapeutics continues to advance its internally developed targeted conditioning program, an anti-CD117 (c-Kit) antibody-drug conjugate (ADC), through preclinical studies. Additionally, CRISPR Therapeutics has ongoing research efforts to enable in vivo editing of hematopoietic stem cells. This work, supported in part by a $14.5 million grant from the Bill & Melinda Gates Foundation, could obviate the need for conditioning altogether, expand geographic reach, and enable the treatment of multiple additional other diseases beyond SCD and TDT.
Immuno-Oncology and Autoimmune Disease

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 CRISPR Therapeutics’ next-generation CAR T product candidates, CTX112 and CTX131, targeting CD19 and CD70, respectively. Emerging pharmacology data, including pharmacokinetics, indicate that the novel potency gene edits in CTX112 and CTX131 can lead to significantly higher CAR T cell expansion and functional persistence in patients compared to the first-generation candidates. Focusing efforts on these candidates will enable the Company to advance these potentially best-in-class CAR T therapies more efficiently and rapidly. The Company expects to provide a clinical update in 2024 for these next-generation candidates.
CRISPR Therapeutics plans to initiate a clinical trial of CTX112 in systemic lupus erythematosus (SLE) in the first half of 2024, with the potential to expand into additional autoimmune indications in the future. Early clinical studies 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 that allogeneic CAR T cells can effectively deplete B cells in clinical trials in oncology settings, which supports the potential of CTX112 in autoimmune diseases.
CRISPR Therapeutics is on track to initiate a Phase 1 trial of CTX131 in hematologic malignancies, including T- and B-cell malignancies, in the first half of 2024. CTX131 is currently in an ongoing clinical trial in solid tumors.
In Vivo

CRISPR Therapeutics continues to advance a pipeline of in vivo gene editing programs using lipid nanoparticle (LNP) delivery of Cas9 mRNA and a guide RNA (gRNA) to the liver. Its first two in vivo programs, CTX310 and CTX320, each aim to reduce expression of a validated target for cardiovascular disease. Beginning with these programs, CRISPR Therapeutics aims to transform the treatment paradigm for cardiovascular indications and beyond with potential one-time therapies that could recapitulate the proven benefit of targets validated by natural human genetics and other therapeutic modalities.
A Phase 1 clinical trial is ongoing for CTX310, targeting angiopoietin-like 3 protein (ANGPTL3). In humans, naturally occurring loss-of-function variants of the ANGPTL3 gene are associated with reduced levels of serum lipids and reduced risk of atherosclerotic cardiovascular disease. The Phase 1 trial is open to patients with mixed dyslipidemias, homozygous familial hypercholesterolemia, heterozygous familial hypercholesterolemia, and severe hypertriglyceridemia.
A Phase 1 clinical trial is ongoing for CTX320, targeting lipoprotein(a) (Lp(a)). Elevated Lp(a), which is associated with an increased risk of atherosclerotic cardiovascular disease, is present in approximately one in five people in the United States and around the world.
CRISPR Therapeutics expects to nominate additional in vivo programs targeting both rare and common diseases this year, to be disclosed in mid-2024.
Regenerative Medicine

CRISPR Therapeutics continues to advance a Phase 1 clinical trial for CTX211 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. Vertex paid $170 million to CRISPR Therapeutics in upfront and milestone payments in 2023 as part of that licensing agreement, and CRISPR Therapeutics remains eligible for an additional $160 million in research and development milestones and would receive royalties on any future products resulting from this agreement.
Other Corporate Matters

In February 2024, CRISPR Therapeutics announced that it has entered into an investment agreement for the sale of approximately $280 million of its common shares to a select group of institutional investors in a registered direct offering, at a price per share of $71.50, representing a premium of greater than 10% to CRISPR Therapeutics’ 30-day volume-weighted average price. The financing is expected to close on or about February 27, 2024, subject to customary closing conditions.
Fourth Quarter and Full Year 2023 Financial Results

Cash Position: Cash, cash equivalents, and marketable securities were $1,695.7 million as of December 31, 2023, compared to $1,868.4 million as of December 31, 2022. The decrease in cash of $172.7 million was primarily driven by operating expenses, offset by payments received from Vertex in connection with a non-exclusive license agreement and related milestone, as well as interest income. Pro-forma cash, cash equivalents, and marketable securities were greater than $2.1 billion as of February 21, 2024, inclusive of a $200 million milestone received in January 2024 for the approval of CASGEVY and approximately $280 million in proceeds from the February 2024 registered direct offering.
R&D Expenses: R&D expenses were $95.1 million for the fourth quarter of 2023, compared to $103.6 million for the fourth quarter of 2022. 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 $16.5 million for the fourth quarter of 2023, compared to $21.2 million for the fourth quarter of 2022. The decrease in G&A expense was primarily driven by a decrease in external professional costs.
Collaboration Expense: Collaboration expense, net, was $20.0 million for the fourth quarter of 2023, compared to $6.8 million for the fourth quarter of 2022. The increase of approximately $13.2 million in collaboration expense, net, was primarily driven by an additional $20 million licensing fee owed to Vertex in connection with the Amended and Restated Joint Development and Collaboration Agreement, offset by the fact that we reached the $110.3 million deferral limit on costs related to the CASGEVY program in the third quarter of 2023, whereas the limit was not reached until the fourth quarter of 2022.
Net Income (Loss): Net income was $89.3 million for the fourth quarter of 2023, compared to a net loss of $110.6 million for the fourth quarter of 2022.
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 through a precise double-strand break. 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 February 20, 2024 Evopoint Biosciences Co., Ltd. (hereinafter referred to as Evopoint) reported the company has successfully completed the Series E funding round with RMB 700 million (Press release, Evopoint Biosciences, FEB 20, 2024, View Source [SID1234656284]). This round of financing was jointly led by one of the leading venture capital firms in China and Guoxin Investment Group, along with the participation of a number of well-known institutions such as Jinan Industrial Development Investment Group, TH Capital, Yuekai Capital, Chenhai Capital, Pudong Venture Capital, and Zhuopu Capital, with the continued support of the old shareholders of Loyal Valley Capital, as well as with Start Point Advisors actingas the exclusive financial advisor for this round of financing.

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The funds raised in this round will mainly be used to promote the domestic and international clinical trials of multiple company pipelines, improve the three major technology platforms of independent innovation of targeted therapy, anti-infection and PROTAC, accelerate the operation of the production base aswell as the construction of the commercialization team, and push for an early product launch to benefit a vast population of patients.

Established in 2017, Evopoint Biosciences is an innovative biopharmaceutical company with extraordinary R&D and commercialization capabilities. Leveraging proprietary discovery platforms for targeted therapy, anti-infective and PROTAC, Evopoint has developed a robust pipeline of clinical assets featuringaβ-lactamase inhibitor, an EZH2 inhibitor, an hURAT1 inhibitor, next-generation ADCs, and many more preclinical programs in focused disease areas including oncology, infectious and metabolic diseases. The company has established multiple out-licensing partnerships with domestic and global pharma companiesto co-develop its assets for global markets. Potential value of these partnerships surpasses billion dollars. Since its inception, Evopoint is committed to improving human health by providing innovative pharmaceutical solutions to address greatest unmet medical needs globally.

Among these, XNW4107 is a new generation of β-lactamase-based broad-spectrumanti-drug-resistant bacterial drug independently developed by Evopoint, with strong antibacterial efficacy against the ever-increasing cases of carbapenem-resistant bacterial infections, such as the Carbapenem-Resistant Acinetobacter baumannii(CRAB), Pseudomonas aeruginosa (CRPA), and Enterobacteriaceae (CRE). This drugis currently undergoing critical, global multicenter Phase III clinical study.

XNW3009, a new generation of uric acid lowering drug, has entered Phase III clinicaltrials, having completed two randomized, double-blind controlled trials. In these two trials, XNW3009’s uric acid lowering effect was respectively shown to be far superior to those of the control groups – benzbromarone and febuxostat, the two drugs with the largest prescription volumes and the highest sales in the current Chinese market.

In the field of oncology, XNW5004, a new generation EZH2 inhibitor, has shown excellent anti-tumor efficacy in hematoma, prostate cancer and other indications, and is currently in Phase II clinical trials. It has entered in to a cooperation with MSD to carry out a clinical trial of co-administration with Keytruda.The new generation ADC drugs XNW27 and XNW28 are in Phase I clinical trials and have demonstrated significantly stronger efficacy and higher therapeutic window potential than competitors with the same target.

Relyingon its stellar product data and external licensing capabilities, Evopoint has entered into a number of external licensing cooperation with well-known companies both domestically and abroad, amounting to billions of USD in total, and is one of the companies that have reached the largest number of "License out"in the domestic biopharmaceutical field.

Since its establishment, the company has been highly recognized by investors, and has introduced domestic and foreign first-tier investment institutions, including Loyal Valley Capital, GIC, Oceanpine Capital, and CICC Capital. Meanwhile, the company has also received strong support from state-owned institutions such as Guoxin Investment Group, Jinan Industrial Development Investment Group, Yuekai Capital, Pudong Venture Capital, Guofa Venture Capital, Zhuopu Capital, and ABC International, and has received a cumulative total of more than RMB 2 billion in financing.

Evopoint will continue to work with determined confidence, maintaining the enthusiasmand motivation that will assemble in to a collective effort to create a better future.

Investment institutions of Series E funding round stated: I am pleased to participate in the Series E funding round of Evopoint. Evopoint is an innovative drug company that focuses on significant unmet clinical needs. Since the last round of funding,the company has demonstrated impressive execution, and several products are about to enter the market validation stage. The company has completed the transition from a "product-based" company to a "platform-based" company, and has built several leading technology platforms. Based on the efficient R&D system and its excellent capabilities, the company is actively going overseas and has completed the "License out" of many overseas pipelines’ interests. We are firmly optimistic about the founding team and product pipeline of Evopoint, and hope that this round of funding can help the products enter the market and benefita vast population of patients.

On February 20, 2024 PharmAbcine, Inc. ("PharmAbcine" or the "Company") (KOSDAQ: 208340), a clinical-stage public company developing next generation therapeutics to treat medical unmet needs, reported that on February 21st, 2023, PharmAbcine received Orphan Drug Designation (ODD) from the U.S. Food and Drug Administration (FDA) for PMC-403 for the treatment of a rare disease, Idiopathic Systemic Capillary Leak Syndrome (ISCLS) (Press release, PharmAbcine, FEB 20, 2024, View Source;bmode=view&idx=18106387&t=board [SID1234649177]).

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PMC-403 is a novel TIE2 binding and activating human IgG with the mechanism of stabilizing pathological and leaky blood vessels. TIE2 receptors, expressed on endothelial cells, are involved in vessel normalization processes such as angiogenesis and intercellular adhesion. PMC-403 activates the TIE2 receptor to improve vascular structure and stabilize abnormal blood vessels. This function has shown potential to be applicable for the treatment of various diseases caused by pathological vasculature.

The Company conducted research collaboration with Dr. Kirk Druey, Chief of the NIH’s Lung and Vascular Inflammation Section, to explore the efficacy of PMC-403 in ISCLS animal models. In this study, PMC-403 demonstrated efficacy in improving survival and alleviating vascular leakage in the mouse model of ISCLS induced by histamine. The study extends to the treatment of mice exposed to influenza, showing promising results in reducing vascular leakage.

ISCLS, or Clarkson Disease, is a severe systemic rare disorder characterized by the sudden and rapid exit of fluids and proteins from blood vessels into surrounding tissues due to the abnormal function of systemic vascular endothelial cells. This leads to symptoms such as hypotension, edema, and hypoalbuminemia, posing a significant threat with a 30% mortality rate upon acute onset.

ODD is a system that encourages the development of treatments for rare diseases or life-threatening diseases with fewer than 200,000 patients in the United States. Through this system, the development of orphan drugs is incentivized by various benefits such as subsidies, tax breaks, and market exclusivity due to the limited patient population, fostering rapid growth in this market. Additionally, the expedited review program for orphan drugs streamlines approval processes, incorporating FDA feedback and enabling faster development through smaller clinical trials.

According to Evaluate Pharma, the global orphan drug market is showing an average annual growth rate of 12%, from approximately $160 billion in 2021 to approximately $280 billion in 2026, and it is expected that orphan drug sales will account for 20% of the total prescription drug market by 2026.

On February 20, 2024, Iovance Biotherapeutics, Inc. (the "Company") reported to have entered into an underwriting agreement (the "Underwriting Agreement") with Jefferies LLC, Barclays Capital Inc. and Goldman Sachs & Co. LLC (collectively, the "Underwriters"), pursuant to which the Company agreed to issue and sell up to 23,014,000 shares of common stock (the "Shares") (the "Offering") (Filing, Iovance Biotherapeutics, FEB 20, 2024, View Source [SID1234640732]). The Shares were offered and sold in the Offering at the offering price of $9.15 per share and were purchased by the Underwriters from the Company at a price of $8.601 per share.

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The Offering was made pursuant to the Company’s effective registration statement on Form S-3 (Registration No. 333-272718), which was previously filed with the U.S. Securities and Exchange Commission under the Securities Act of 1933, as amended (the "Securities Act").

The Company estimates that the net proceeds from the Offering, after deducting the underwriting discounts and commissions and estimated offering expenses payable by the Company, will be approximately $197.1 million. The Company intends to use the net proceeds from the Offering to support the commercial launch of AMTAGVITM, to fund ongoing clinical programs including the Company’s NSCLC registration-directed study, IOV-LUN-202, and its frontline advanced melanoma Phase 3 confirmatory trial, TILVANCE-301, to continue the development of the Company’s pipeline candidates, and for other general corporate purposes.

The Offering is expected to close on February 22, 2024, subject to customary closing conditions. In the Underwriting Agreement, the Company made customary representations, warranties and covenants and also agreed to indemnify the Underwriters against certain liabilities, including liabilities under the Securities Act, or to contribute to payments that the Underwriters may be required to make because of such liabilities.

Pursuant to the Underwriting Agreement, the Company’s executive officers and directors entered into agreements in substantially the form included as an exhibit to the Underwriting Agreement filed hereto, providing for a 60-day "lock-up" period with respect to sales of the Company’s common stock, subject to certain exceptions.

The foregoing is a summary description of the Underwriting Agreement and is qualified in its entirety by the text of the Underwriting Agreement attached as Exhibit 1.1 to this Current Report on Form 8-K and incorporated herein by reference.