On March 28, 2024 Clarity Pharmaceuticals (ASX: CU6) ("Clarity", "the Company"), a clinical stage radiopharmaceutical company with a mission to develop next-generation products that improve treatment outcomes for children and adults with cancer, reported the successful completion of a $101 million placement to institutional investors ("Placement") and the institutional component (the "Institutional Entitlement Offer") of the approximate $20 million pro rata accelerated non-renounceable entitlement offer to existing eligible Clarity shareholders in Australia and New Zealand ("Entitlement Offer") (the Entitlement Offer and the Placement, collectively the "Offer") (Press release, Clarity Pharmaceuticals, MAR 28, 2024, View Source [SID1234641559]).

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The Placement and Institutional Entitlement Offer closed on Tuesday, 26 March 2024. The offer price per new fully paid ordinary share in Clarity ("New Share") to be issued under the Offer is $2.55 per New Share ("Offer Price").

Bell Potter ("Underwriter") is the sole underwriter and is acting as joint lead manager with Wilsons Corporate Finance ("Joint Lead Managers"), with Lander & Rogers the Australian legal adviser.

COMPLETION OF PLACEMENT AND INSTITUTIONAL ENTITLEMENT OFFER
The Placement will result in the issue of approximately 39.5 million New Shares at the Offer Price, raising approximately $101 million. Approximately 3.7 million New Shares will be issued to successful applicants under the Institutional Entitlement Offer at the Offer Price, raising approximately $9 million. The Placement and Institutional Entitlement Offer were well supported by new and existing institutional investors, including specialist healthcare investors.

As outlined in the Company’s announcement on Tuesday, 26 March 2024, funds raised under the Offer will be used to advance Clarity’s clinical portfolio and strengthen its balance sheet. The amounts raised will fund the development of Clarity’s clinical portfolio of products, SAR-bisPSMA, SAR-Bombesin and SARTATE, as the Company progresses towards a number of clinical trial milestones. Please refer to Clarity’s investor presentation for further details.

As a result of the successful completion of the Placement and Institutional Entitlement Offer, Clarity’s ordinary shares (the "Shares") are expected to recommence normal trading on an ex-entitlement basis from the opening of the market on Thursday, 28 March 2024.

New Shares subscribed for under the Institutional Entitlement Offer and Placement are expected to be settled on Friday, 5 April 2024, to be issued and commence trading on ASX on Monday, 8 April 2024. New Shares issued pursuant to the Institutional Entitlement Offer and Placement will rank equally with existing Shares on issue with effect from their date of issue.

Clarity’s Executive Chairperson, Dr Alan Taylor, commented: "It is great to see the incredible response to the capital raising from existing and new shareholders alike, and we thank our shareholders for their continued support in building Clarity into an Australian life sciences success story. The total of $121 million significantly strengthens our balance sheet to over $150 million and allows us to continue to progress all of our products through their respective clinical trials. This is the first capital raising after the completion of the Company’s record $92 million IPO capital raising on the ASX in August 2021 and we are now very well positioned to maximise the value of our Company in what has become one of the most exciting areas of the pharmaceutical industry, radiopharmaceuticals.

"While big pharmaceutical companies are on the hunt for new clinical-stage radiopharmaceutical assets, we continue to differentiate from the current generation of products. What makes Clarity stand out from a myriad of other radiopharmaceuticals is not only the remarkable data on all three of our Targeted Copper Theranostic (TCT) products in clinical development to date, but also TCTs’ ability to resolve the logistical and manufacturing limitations of the current generation of products and expand the field into the large oncology market. TCTs are scalable, sustainable and dependable, removing reliance on the antiquated fleet of nuclear reactors and short shelf life products.

"Once again, we thank our shareholders for their support, and welcome our new shareholders to the Clarity story. We look forward to further updating our shareholders shortly on the continued progress of our therapy and diagnostic programs as we head towards our ultimate goal of better treating children and adults with cancer."

RETAIL ENTITLEMENT OFFER
Eligible Retail Shareholders (defined below) who have a registered address in Australia or New Zealand as at 7.00pm (Sydney time) on Thursday, 28 March 2024 (the "Record Date") are invited to participate in the retail component of the Entitlement Offer at the Offer Price (the "Retail Entitlement Offer").

Eligible Retail Shareholders are shareholders on the Record Date who are already registered as holders of Shares at the Record Date and:

have a registered address on the Clarity register of members which is in Australia or New Zealand;
are not in the United States nor acting for the account or benefit of a person in the United States;
were not invited to participate in the Institutional Entitlement Offer and were not treated as an ineligible institutional shareholder under the Institutional Entitlement Offer (other than as nominee or custodian, in each case in respect of other underlying holdings); and
are eligible under all applicable securities laws to receive an offer under the Retail Entitlement Offer (the "Eligible Retail Shareholders").
The Retail Entitlement Offer will raise up to approximately $11 million. The Retail Entitlement Offer is expected to open on Thursday, 4 April 2024 and close at 5.00pm (Sydney time) on Friday, 19 April 2024 (the "Retail Entitlement Offer Period").

Further information will be sent to Eligible Retail Shareholders via a shareholder letter to be dispatched on or around Thursday, 4 April 2024 and further information will also be available in the offer booklet for the Retail Entitlement Offer (the "Retail Offer Booklet") which is expected to be lodged with ASX and made available on the ASX website (www.asx.com.au) on or around Thursday, 4 April 2024.

The Retail Offer Booklet and accompanying personalised entitlement and acceptance form ("Application Form") will contain instructions for Eligible Retail Shareholders on how they can apply for New Shares as part of the Retail Entitlement Offer.

Application Forms and payments are due by no later than 5.00pm (Sydney time) on Friday, 19 April 2024 unless otherwise extended at the discretion of Clarity’s Board of Directors and in compliance with ASX Listing Rules.

Shortfall
If there is any shortfall under the Retail Entitlement Offer which is not acquired by the Underwriter (i.e. if the Underwriting Agreement were to be terminated), Clarity’s directors reserve the right to place any or all of the shortfall to one or more investors within three months of the closing date of the Retail Entitlement Offer, at the directors’ discretion and at a price not less than the Offer Price.

Indicative Timetable
Event Date (2024)
Results of Placement and Institutional Entitlement Offer announced; Trading Halt ceases 28 March
Record Date for the Retail Entitlement Offer 7.00pm, 28 March
Retail Entitlement Offer materials dispatched to Eligible Retail Shareholders 4 April
Retail Entitlement Offer opens 4 April
Placement and Institutional Entitlement Offer settlement date 5 April
Issue and quotation of New Shares under Placement and Institutional Entitlement Offer 8 April
Retail Entitlement Offer closes (Retail Closing Date) 5:00pm, 19 April
Announcement of results of the Retail Entitlement Offer 24 April
Settlement of New Shares issued under the Retail Entitlement Offer 26 April
Issue of New Shares under the Retail Entitlement Offer 29 April
Quotation and trading commence on a normal settlement basis 30 April
The above timetable is indicative only (except where historical) and subject to change. All times and dates refer to Sydney time. Subject to the ASX Listing Rules, Clarity in conjunction with the Joint Lead Managers reserves the right to vary any or all of these dates, including the Retail Closing Date, without prior notice or consultation with you. Any extension of the Retail Closing Date will have a consequential effect on the anticipated date for issue of the New Shares under the Retail Entitlement Offer. The Directors also reserve the right not to proceed with the whole or part of any of the Offer at any time prior to allotment of the New Shares. In that event, the relevant Application Monies will be returned without interest.

Shareholder Enquiries
Eligible Retail Shareholders who have questions relating to the Retail Entitlement Offer should call Clarity’s share registry, Link Market Services Limited, on 1300 494 861 (within Australia) or + 61 1300 494 861 (from outside Australia) from 8.30am to 5.30pm (Sydney time) Monday to Friday during the Retail Entitlement Offer Period.

Further information in relation to the Placement and the Entitlement Offer is set out in an investor presentation which Clarity filed with the ASX on Tuesday, 26 March 2024. The investor presentation contains important information including key risks and assumptions and foreign selling restrictions with respect to the Placement.

ADDITIONAL INFORMATION
This announcement has been authorised and approved by the Board of Directors of Clarity for lodgement with ASX.

All the amounts are in Australian dollars unless otherwise indicated.

On March 28, 2024 Candel Therapeutics, Inc. (Candel or the Company) (Nasdaq: CADL), a clinical stage biopharmaceutical company focused on developing multimodal biological immunotherapies to help patients fight cancer, reported financial results for the fourth quarter and year ended December 31, 2023, and provided a corporate update (Press release, Candel Therapeutics, MAR 28, 2024, View Source [SID1234641558]).

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"2023 was a significant year for Candel with two additional FDA Fast Track Designations for CAN-2409 for non-small cell lung cancer and borderline resectable pancreatic cancer, and most recently Candel received FDA Fast Track Designation for CAN-3110 for recurrent high-grade glioma in February of 2024. We are also excited that initial results in CAN-3110’s ongoing phase 1b clinical trial were published in the high-impact scientific journal, Nature," said Paul Peter Tak, MD PhD FMedSci, President and CEO of Candel. "Further, initial patient data showed improved survival after experimental treatment with Candel’s investigational viral multimodal immunotherapies, as compared to standard of care, in non-small cell lung cancer (CAN-2409), pancreatic cancer (CAN-2409), and high-grade glioma (CAN-3110)."

Dr. Tak continued, "In 2024, we are expecting six data readouts across our three platforms, which include novel clinical and biomarker data in lung cancer, pancreatic cancer, and brain cancer, and a potentially registrational phase 3 clinical trial in prostate cancer. We look forward to sharing additional updates in the year ahead."

Fourth Quarter 2023 & Recent Highlights

o
CAN-2409 – Pancreatic Cancer

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Announced initial positive interim data from our randomized phase 2 clinical trial of CAN-2409 in non-metastatic pancreatic cancer which showed prolonged and sustained survival, robust activation of immune response after dosing of CAN-2409, and a favorable tolerability profile.

▪
U.S. Food and Drug Administration (FDA) granted Fast Track Designation for CAN-2409 plus prodrug (valacyclovir) for the treatment of patients with pancreatic ductal adenocarcinoma to improve overall survival (OS).
o
CAN-3110 – Recurrent High-Grade Glioma (HGG)
▪
The results from the ongoing first-in-human phase 1b clinical trial of CAN-3110 in recurrent high-grade glioma, showing extended survival associated with immune activation, were published online on October 18, 2023, in Nature.
▪
FDA granted Fast Track Designation to CAN-3110 for the treatment of patients with recurrent high-grade glioma (HGG) to improve OS.
o
enLIGHTEN Discovery Platform CAN-2409 – Pancreatic Cancer

▪
Presented encouraging preclinical data from the first experimental candidate from its discovery pipeline, Alpha 201-macro-1, at both the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) and the International Oncolytic Virus Conference (IOVC) in November 2023. This investigational, locally delivered, biological oncolytic therapeutic, which is designed to interfere with the CD47/SIRP1a pathway, demonstrated better inhibition of tumor growth, when compared to systemic anti-CD47 antibody therapy, in a mouse model of breast cancer.

▪
Announced an upcoming "late-breaking" poster presentation at the 2024 AACR (Free AACR Whitepaper) Annual Meeting unveiling the second drug candidate from the enLIGHTEN Discovery Platform.

Anticipated Milestones

o
New preclinical data on the second drug candidate from the enLIGHTEN Discovery Platform to be presented at the 2024 AACR (Free AACR Whitepaper) Annual Meeting taking place April 5-10, 2024
o
Phase 2 topline OS data for CAN-2409 in NSCLC expected in Q2 2024
o
Phase 2 updated OS data for CAN-2409 in borderline resectable pancreatic cancer expected in Q2 2024
o
Phase 2 topline data for CAN-2409 in low-to-intermediate-risk, localized, non-metastatic prostate cancer expected in Q4 2024
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Phase 3 topline data for CAN-2409 in localized intermediate/high-risk prostate cancer expected in Q4 2024

Financial Results for the Year and Fourth Quarter Ended December 31, 2023

Research and Development Service Revenue, related party: Research and development service revenue, related party, for each of the quarter and full year ended December 31, 2023 was $0, as compared to $31,000 and $125,000 for the quarter and full year ended December 31, 2022.

Research and Development Expenses: Research and development expenses were $7.3 million for the fourth quarter of 2023 compared to $5.0 million for the fourth quarter of 2022, and $24.5 million for the full year 2023 compared to $20.8 million for the full year 2022. The increase was primarily due to manufacturing and regulatory activities in support of the Company’s CAN-2409 programs, stock compensation costs, and impairment of fixed assets. Research and development expenses included non-cash stock compensation expense of $0.5 million and $1.3 million for the fourth quarter and full year of 2023, respectively, as compared to a non-cash stock compensation expense of $0.2 million and $0.8 million for the fourth quarter and full year of 2022.

General and Administrative Expenses: General and administrative expenses were $3.1 million for the fourth quarter of 2023 compared to $3.2 million for the fourth quarter of 2022, and $13.9 million for the full year 2023 compared to $14.1 million for the full year 2022. The decrease was primarily due to lower insurance and recruiting costs, which were partially offset by increased employee-related expenses. General and administrative expenses included non-cash stock compensation expense of $0.5 million and $1.7 million for the fourth quarter and full year of 2023, respectively, as compared to a non-cash stock compensation expense of $0.4 million and $1.5 million for the fourth quarter and full year of 2022.

Net Loss: Net loss for the fourth quarter of 2023 was $11.1 million compared to a net loss of $5.1 million for the fourth quarter of 2022, and included net other expense of $0.8 million and net other income $3.0 million, respectively. The change from net other income in the fourth quarter of 2022 to net other expense in the fourth quarter of 2023 was primarily related to the change in the fair value of the Company’s warrant liability. Net loss for the full year 2023 was $37.9 million compared to a net loss of $18.8 million for the full year 2022, and included net other income of $0.5 million and $15.9 million, respectively, related primarily to the change in the fair value of the Company’s warrant liability.

Cash Position: Cash and cash equivalents as of December 31, 2023 were $35.4 million, as compared to $70.1 million as of December 31, 2022. Based on current plans and assumptions, the Company expects that its existing cash and cash equivalents will be sufficient to fund its current operating plan into the fourth quarter of 2024.

On March 28, 2024 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE: CANF), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address oncological and inflammatory diseases, reported financial results and clinical updates for the twelve months ended December 31, 2023 (Press release, Can-Fite BioPharma, MAR 28, 2024, View Source [SID1234641557]).

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Recent Clinical & Development Milestones Achieved

Namodenoson Drug Candidate:

1. Ewopharma recently acquired marketing rights for Namodenoson in the treatment of pancreatic carcinoma This adds up to an out licensing agreement that Can-Fite signed with Switzerland-based Ewopharma in 2021, for exclusive distribution of both Piclidenoson and Namodenoson in Central Eastern European (CEE) countries (Piclidenoson for the treatment of psoriasis and Namodenoson for the treatment of liver cancer and NASH). Under the terms of the distribution agreement, Ewopharma AG paid Can-Fite an upfront payment of US$2.25 million with up to an additional US$40.45 million, payable upon the achievement of regulatory and sales milestones, plus 17.5% royalties on net sales. Recently, Ewopharma AG exercised its right to expand the distribution agreement to include the indication of pancreatic cancer and the transaction terms of the distribution agreement are applicable to such indication.

2. Can-Fite Broadens its Strong Intellectual Property (IP) for NASH (MASH): Received Patent Allowance in Canada

Can-Fite received a Notice of Allowance from the Canadian Intellectual Property Office for its patent application titled "An A3 Adenosine Receptor Ligand For Use In Treating Ectopic Fat Accumulation". This invention addresses the use of Namodenoson for the reduction of liver fat in patients with NASH a clinical indication that is being developed by Can-Fite. In a successfully concluded Phase IIa study, Namodenoson, one of the Company’s two drugs in advanced clinical development, reduced liver fat content, showed anti-inflammatory effects manifested by a significant decrease in the liver enzymes ALT & AST, and decreased body weight in patients with NASH. A Company-sponsored study for Namodenoson for this indication is currently enrolling patients for a Phase IIb study which will include 140 patients, in whom liver pathology is the primary endpoint. Patent has already been issued in other major markets including the U.S., EU, Japan and China.

Piclidenoson Drug Candidate:

Positive Data from the COMFORT-1 Phase III Psoriasis Study Published in a Top Scientific Journal The Journal of the European Academy of Dermatology and Venereology (EADV) published an article titled "Efficacy and safety of piclidenoson in plaque psoriasis: Results from a randomized phase 3 clinical trial (COMFORT-1)". EADV is a top ranked peer reviewed journal (impact factor 9.2) that publishes articles on clinical and basic science topics in dermatology. The article’s first author, Dr. K.A Papp, is an internationally renowned key opinion leader in the psoriasis field and was the engine for some registered drugs on the market for this devastating skin disease. The EADV article presents the safety and efficacy of Piclidenoson in the randomized, placebo- and active-controlled, double-blind Phase III COMFORT-1 trial. As previously reported, the study met its primary endpoint which was the proportion of patients achieving ≥75% improvement in Psoriasis Area and Severity Index (PASI) from baseline (PASI-75) at Week 16 (3 mg BID dose: PASI 75 rate of 9.7% vs. 2.6% for Piclidenoson vs. placebo, p=0.037). Piclidenoson’s efficacy continued to increase throughout the study period in a linear manner with an excellent safety and tolerability profile. Currently, Piclidenoson is being evaluated in COMFORT-2 a pivotal Phase III study that has been approved by both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

"Our advanced-stage pipeline continues to achieve milestones, with Piclidenoson and Namodenoson both positioned as potentially safe and effective treatments for the oncological diseases liver cancer & pancreatic carcinoma and the inflammatory and metabolic diseases psoriasis and NASH. We anticipate additional clinical progress and new out licensing deals in this year," stated Can-Fite CEO Motti Farbstein.

Financial Results

Revenues for the year ended December 31, 2023 were $0.74 million, a decrease of $0.07 million, or 8.6%, compared to $0.81 million for the year ended December 31, 2022. The decrease in revenues was mainly due to the recognition a lower portion of advance payments received under the Ewopharma distribution agreement entered in 2021 and a lower portion of advance payments received under distribution agreements from Gebro, Chong Kun Dung Pharmaceuticals, and Cipher Pharmaceuticals.

Research and development expenses for the year ended December 31, 2023 were $5.98 million, a decrease of $1.78 million, or 22.9%, compared to $7.76 million for the year ended December 31, 2022. Research and development expenses for the year ended December 31, 2023 comprised primarily of expenses associated with the completion of the Phase 3 study of Piclidenoson for the treatment of psoriasis and two ongoing studies for Namodenoson, a Phase 3 study in the treatment of advanced liver cancer and a Phase 2b study for NASH. The decrease is primarily due to a decrease in expenses associated with Piclidenosnon.

General and administrative expenses were $2.95 million for the year ended December 31, 2023 a decrease of $0.19 million, or 6.05%, compared to $3.14 million for the year ended December 31, 2022. The decrease is primarily due to the decrease in directors and officer’s insurance policy premium. We expect that general and administrative expenses will remain at the same level through 2024.

Financial income (expense), net for the year ended December 31, 2023 aggregated $0.56 million compared to financial expense, net of $(0.07) for the year ended December 31, 2022. The decrease in financial expense, net was mainly due to increase interest from deposits and reduction in expenses related to the revaluation of our short-term investment.

Net loss for the year ended December 31, 2023 was $7.63 million compared with a net loss of $10.17 million for the same period in 2022. The decrease in net loss for the year ended December 31, 2023 was primarily attributable to the decrease in research and development expenses and in general and administrative expenses.

As of December 31, 2023, Can-Fite had cash and cash equivalents and short term deposits of $8.90 million as compared to $7.98 million at December 31, 2022. The decrease in cash during the year ended December 31, 2023 is due to the ongoing operations of the Company which was offset by the Company’s financing during January 2023 and exercise of certain warrants during November 2023.

The Company’s consolidated financial results for the year ended December 31, 2023 are presented in accordance with US GAAP Reporting Standards.

More detailed information can be found in the Company’s Annual Report on Form 20-F for the fiscal year ended December 31, 2023, a copy of which has been filed with the Securities and Exchange Commission (SEC). The Annual Report, which contains the Company’s audited consolidated financial statements, can be accessed on the SEC’s website at View Source as well as via the Company’s investor relations website at View Source The Company will deliver a hard copy of its Annual Report, including its complete audited consolidated financial statements, free of charge, to its shareholders upon request to Can-Fite Investor Relations at 26 Ben Gurion Street, Ramat Gan, 5257346, Israel or by phone at +972-3-9241114.

On March 28, 2024 Bristol Myers Squibb (NYSE: BMY) reported that the pivotal Phase 3 KRYSTAL-12 study, evaluating KRAZATI (adagrasib) as a monotherapy in patients with pretreated locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring a KRASG12C mutation, met the primary endpoint of progression-free survival (PFS) and the key secondary endpoint of overall response rate (ORR) as assessed by Blinded Independent Central Review (BICR) at final analysis for these endpoints (Press release, Bristol-Myers Squibb, MAR 28, 2024, View Source [SID1234641556]). The study remains ongoing to assess the additional key secondary endpoint of overall survival. Results of the confirmatory trial showed that KRAZATI demonstrated a statistically significant and clinically meaningful benefit in PFS and ORR compared to standard-of-care chemotherapy as a second-line or later treatment for these patients. KRAZATI had no new safety signals and the safety data was consistent with the known safety profile.

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"Today’s news is an important reinforcement of the power of a targeted therapy for patients with locally advanced or metastatic KRASG12C-mutated lung cancer. FDA approval of KRAZATI in the U.S. has allowed us to provide a new treatment option for these patients, and topline results of the KRYSTAL-12 confirmatory study will build greater trust in the medical and patient community," said Abderrahim Oukessou, M.D., vice president, global program lead, KRAZATI, Bristol Myers Squibb. "We are encouraged by the results from KRYSTAL-12 and look forward to helping more patients with KRASG12C-mutated lung cancer."

The company will complete a full evaluation of the available data and looks forward to sharing the results with the scientific community at an upcoming medical conference as well as discussing the results with health authorities.

The U.S. FDA granted accelerated approval for KRAZATI as a targeted treatment for patients with KRASG12C-mutated locally advanced or metastatic NSCLC who have received at least one prior systemic therapy in December 2022. In 2023, Medicines and Healthcare products Regulatory Agency (MHRA) granted conditional marketing authorization for KRAZATI as a targeted treatment option for adult patients with KRASG12C-mutated advanced NSCLC and disease progression after at least one prior systemic therapy followed by the European Commission (EC) in 2024.

In addition to KRASG12C-mutated NSCLC, KRAZATI and KRAZATI-based combinations have shown encouraging meaningful benefit in Phase 2 clinical trials across several tumors, including advanced colorectal cancer, pancreatic cancer and other solid tumors. In February, the U.S. FDA accepted for priority review the supplemental new drug application (sNDA) for KRAZATI in combination with cetuximab for the treatment of patients with previously treated KRASG12C-mutated locally advanced or metastatic colorectal cancer (CRC). The FDA assigned a Prescription Drug User Fee Act (PDUFA) goal date of June 21, 2024.

Bristol Myers Squibb thanks the patients and investigators involved in the KRYSTAL-12 clinical trial.

ABOUT KRAZATI (adagrasib)

KRAZATI (adagrasib) is highly selective and potent oral small-molecule inhibitor of KRASG12C that is optimized to sustain target inhibition, an attribute that could be important to treat KRASG12C-mutated cancers, as the KRAS protein regenerates every 24-48 hours. KRASG12C mutations act as oncogenic drivers and occur in approximately 14% of non-small cell lung cancer, 3-4% of colorectal cancer, and 1-2% of several other cancers.

In 2022, KRAZATI was granted accelerated approval for treatment of adult patients with KRASG12C-mutated locally advanced or metastatic NSCLC, as determined by an FDA-approved test, who have received at least one prior systemic therapy. This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial(s).

In 2023, Medicines and Healthcare products Regulatory Agency (MHRA) granted conditional marketing authorization for KRAZATI as a targeted treatment option for adult patients with KRASG12C-mutated advanced non-small cell lung cancer and disease progression after at least one prior systemic therapy followed by the European Commission (EC) in 2024.

KRAZATI continues to be evaluated as monotherapy and in combination with other anti-cancer therapies in patients with advanced KRASG12C-mutated solid tumors, including non-small cell lung cancer and colorectal cancer.

In 2022, the FDA granted breakthrough therapy designation for KRAZATI in combination with cetuximab in patients with KRASG12C-mutated advanced colorectal cancer whose cancer has progressed following prior treatment with chemotherapy and an anti-VEGF therapy.

For Prescribing Information, visit KRAZATI.

About KRYSTAL-12

KRYSTAL-12 is an open-label, multicenter, randomized Phase 3 study evaluating KRAZATI compared to standard-of-care chemotherapy alone, in patients with KRASG12C-mutated non-small cell lung cancer. The primary endpoint of the study is PFS as assessed by BICR. Secondary endpoints included overall survival (OS), overall response rate (ORR), duration of response (DOR), and safety.

INDICATION

KRAZATI is indicated for the treatment of adult patients with KRASG12C-mutated locally advanced or metastatic non-small cell lung cancer, as determined by an FDA-approved test, who have received at least one prior systemic therapy.

This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial(s).

IMPORTANT SAFETY INFORMATION

GASTROINTESTINAL ADVERSE REACTIONS

In the pooled safety population, serious gastrointestinal adverse reactions observed were gastrointestinal obstruction in 1.6%, including 1.4% grade 3 or 4, gastrointestinal bleeding in 0.5% of patients, including 0.5% grade 3, and colitis in 0.3%, including 0.3% grade 3. In addition, nausea, diarrhea, or vomiting occurred in 89% of 366 patients, including 9% grade 3. Nausea, diarrhea, or vomiting led to dosage interruption or dose reduction in 29% of patients and permanent discontinuation of KRAZATI in 0.3%
Monitor and manage patients using supportive care, including antidiarrheals, antiemetics, or fluid replacement, as indicated. Withhold, reduce the dose, or permanently discontinue KRAZATI based on severity
QTC INTERVAL PROLONGATION

KRAZATI can cause QTc interval prolongation, which can increase the risk for ventricular tachyarrhythmias (eg, torsades de pointes) or sudden death
In the pooled safety population, 6% of 366 patients with at least one post-baseline electrocardiogram (ECG) assessment had an average QTc ≥501 ms, and 11% of patients had an increase from baseline of QTc >60 msec. KRAZATI causes concentration-dependent increases in the QTc interval
Avoid concomitant use of KRAZATI with other products with a known potential to prolong the QTc interval. Avoid use of KRAZATI in patients with congenital long QT syndrome and in patients with concurrent QTc prolongation
Monitor ECGs and electrolytes prior to starting KRAZATI, during concomitant use, and as clinically indicated in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, and in patients who are taking medications that are known to prolong the QT interval. Withhold, reduce the dose, or permanently discontinue KRAZATI, depending on severity
HEPATOTOXICITY

KRAZATI can cause hepatotoxicity
In the pooled safety population, hepatotoxicity occurred in 37%, and 7% were grade 3 or 4. A total of 32% of patients who received KRAZATI had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); 5% were grade 3 and 0.5% were grade 4. Increased ALT/AST leading to dose interruption or reduction occurred in 11% of patients. KRAZATI was discontinued due to increased ALT/AST in 0.5% of patients
Monitor liver laboratory tests (AST, ALT, alkaline phosphatase, and total bilirubin) prior to the start of KRAZATI, and monthly for 3 months or as clinically indicated, with more frequent testing in patients who develop transaminase elevations. Reduce the dose, withhold, or permanently discontinue KRAZATI based on severity
INTERSTITIAL LUNG DISEASE /PNEUMONITIS

KRAZATI can cause interstitial lung disease (ILD)/pneumonitis, which can be fatal. In the pooled safety population, ILD/pneumonitis occurred in 4.1% of patients, 1.4% were grade 3 or 4, and 1 case was fatal. The median time to first onset for ILD/pneumonitis was 12 weeks (range: 5 to 31 weeks). KRAZATI was discontinued due to ILD/pneumonitis in 0.8% of patients
Monitor patients for new or worsening respiratory symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, fever). Withhold KRAZATI in patients with suspected ILD/pneumonitis and permanently discontinue KRAZATI if no other potential causes of ILD/pneumonitis are identified
ADVERSE REACTIONS

The most common adverse reactions (≥25%) are nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, renal impairment, edema, dyspnea, decreased appetite
FEMALES AND MALES OF REPRODUCTIVE POTENTIAL

Infertility: Based on findings from animal studies, KRAZATI may impair fertility in females and males of reproductive potential
Please see U.S. Full Prescribing Information for KRAZATI.

On March 28, 2024 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leader in T-cell immunotherapy, leveraging its novel allogeneic Epstein-Barr virus (EBV) T-cell platform to develop transformative therapies for patients with cancer and autoimmune diseases, reported financial results for the fourth quarter and full year 2023, recent business highlights, and key upcoming milestones for 2024 (Press release, Atara Biotherapeutics, MAR 28, 2024, View Source [SID1234641555]).

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"We are expanding Atara’s proven EBV T-cell platform into allogeneic CAR T therapy for both oncology and autoimmune disease," said Pascal Touchon, President and Chief Executive Officer of Atara. "This includes strong momentum for our lead CAR T program, ATA3219, which is positioned to deliver near-term clinical data for both non-Hodgkin’s lymphoma and lupus nephritis. We also are focused on submitting our BLA for tab-cel in the second quarter, the progress of which triggers financial milestones and sales royalty opportunities in our partnership with Pierre Fabre."

Tabelecleucel (tab-cel or EbvalloTM) for Post-Transplant Lymphoproliferative Disease (PTLD)

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Atara recently held a positive pre-BLA meeting with the U.S. Food and Drug Administration (FDA) that supports its plan to submit the tab-cel relapsed or refractory Epstein-Barr virus positive post-transplant lymphoproliferative disease (EBV+ PTLD) Biologics License Application (BLA) in Q2 2024
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Data from the pivotal Phase 3 ALLELE study of tab-cel were published in The Lancet Oncology and showed a significant 51.2% objective response rate (ORR) and 23.0-month median duration of response in relapsed or refractory EBV+ PTLD subjects. Tab-cel was well tolerated with no events of graft-versus-host disease related to tab-cel
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Positive new data presented at the 2023 ESMO (Free ESMO Whitepaper)-IO meeting from the actively enrolling, multicohort Phase 2 EBVision trial with a pooled analysis demonstrated a 77.8% ORR in 18 central nervous system (CNS) EBV+ PTLD subjects including front line EBV+ PTLD
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Atara and Pierre Fabre Laboratories closed the expanded global partnership in December 2023 for the development, manufacturing, and commercialization rights of tab-cel in the United States and all remaining markets
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Atara received approximately $27 million in cash upfront at the closing of the deal. Under the agreement, Atara has the potential to receive up to $640 million in additional payments and significant double-digit tiered royalties on net sales, including up to $100 million in potential regulatory milestones through BLA approval
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Atara expects to receive $20 million of these regulatory milestones in April based on the recent positive pre-BLA meeting, another $20 million in connection with BLA acceptance, and the remaining $60 million in potential regulatory milestones in connection with BLA approval

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In addition, Pierre Fabre Laboratories will reimburse Atara for tab-cel regulatory and development costs through BLA approval, and purchase tab-cel inventory manufactured through BLA transfer

ATA3219: CD19 Program in Lupus Nephritis

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Investigational New Drug (IND) application cleared for the use of ATA3219 as a monotherapy for the treatment of systemic lupus erythematosus (SLE) with kidney involvement (lupus nephritis [LN])
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Atara plans to initiate a Phase 1 LN study in H2 2024 with initial clinical data anticipated H1 2025
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The Phase 1 open-label, dose-escalation study is designed to evaluate safety, preliminary efficacy, pharmacokinetics, and biomarkers of a single dose of ATA3219 administered to LN subjects refractory to one or more lines of treatment. Subjects will receive lymphodepletion (LD) treatment followed by ATA3219 at a dose of 40, 80, or 160 x 106 CAR+ T cells. Each dose level is designed to enroll 3-6 patients
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In vitro data demonstrated the CD19 antigen-specific functional activity of ATA3219 and CAR-mediated activity against B cells from SLE patients. ATA3219 led to near-complete CD19-specific B-cell depletion compared to controls. These preclinical data were submitted as part of a late-breaking abstract which was accepted for poster presentation at the upcoming International Society for Cell & Gene Therapy meeting held May 29-June 1, 2024

ATA3219: CD19 Program in Non-Hodgkin’s Lymphoma (NHL)

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Atara initiated enrollment of a multi-center, Phase 1 open-label, dose-escalation clinical trial of ATA3219 in NHL, including large B-cell lymphomas, follicular lymphoma, and mantle cell lymphoma, with initial clinical data anticipated in Q4 2024
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Study designed to evaluate safety, preliminary efficacy, pharmacokinetics, and biomarkers. Subjects will receive LD treatment followed by ATA3219 at a dose of 40, 80, 240, or 480 x 106 CAR+ T cells. Each dose level is designed to enroll 3-6 patients
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Preclinical data previously presented demonstrated superior in vivo persistence and CD19-specific anti-tumor efficacy compared to an autologous CD19 CAR T benchmark with no observed toxicity or alloreactivity

ATA3431: CD19/CD20 Program for B-Cell Malignancies

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Preclinical data presented at ASH (Free ASH Whitepaper) 2023 demonstrated early evidence of potent antitumor activity, long-term persistence, and superior tumor growth inhibition compared to an autologous CD19/CD20 CAR T benchmark
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Dual CD19 and CD20 targeting designed to address CD19 escape and tumor variability and may provide additional efficacy in lymphoma
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Atara is progressing toward an IND submission in 2025

Fourth Quarter and Full Year 2023 Financial Results

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Cash, cash equivalents and short-term investments as of December 31, 2023 totaled $51.7 million, as compared to $102.4 million as of September 30, 2023 and $242.8 million as of December 31, 2022
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Net cash used in operating activities was $50.4 million and $193.0 million for the fourth quarter and fiscal year 2023, as compared to $56.9 million and $270.4 million in the same periods in 2022

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Atara reported net losses of $60.5 million, or $0.56 per share, and $276.1 million, or $2.61 per share, for the fourth quarter and fiscal year 2023, respectively, as compared to $74.6 million, or $0.72 per share, and $228.3 million, or $2.24 per share, for the same periods in 2022
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Total costs and operating expenses include non-cash stock-based compensation, depreciation and amortization expenses of $11.1 million and $50.2 million for the fourth quarter and fiscal year 2023, respectively, as compared to $12.6 million and $59.5 million for the same periods in 2022
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Total costs and operating expenses include restructuring expense of $6.7 million for the fourth quarter and fiscal year 2023 related to the reduction in force Atara announced in November 2023 and which reduced its headcount at that time by approximately 30%. This reduction in force was substantially completed in December 2023
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Atara announced an additional reduction in force in January 2024 that further reduced its headcount by approximately 25% to approximately 170 employees
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Research and development expenses were $49.6 million and $224.8 million for the fourth quarter and fiscal year 2023, respectively, as compared to $62.5 million and $272.5 million for the same periods in 2022
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Research and development expenses include $5.8 million and $26.5 million of non-cash stock-based compensation expenses for the fourth quarter and fiscal year 2023, respectively, as compared to $7.0 million and $31.4 million for the same periods in 2022
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General and administrative expenses were $11.5 million and $50.9 million for the fourth quarter and fiscal year 2023, respectively, as compared to $13.2 million and $71.6 million for the same periods in 2022
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General and administrative expenses include $4.1 million and $18.9 million of non-cash stock-based compensation expenses for the fourth quarter and fiscal year 2023, respectively, as compared to $4.4 million and $22.5 million for the same periods in 2022

2024 Outlook and Cash Runway

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The cash, cash equivalents and short-term investments of $51.7 million as of December 31, 2023 does not include the approximately $27 million received in January 2024 from Pierre Fabre Laboratories from the closing of the expanded global partnership, the approximately $15 million in proceeds from the issuance of pre-funded warrants received in the Company’s January 2024 registered direct offering, or the approximately $10 million in proceeds from the Company’s at-the-market facility (ATM) received in Q1 2024. The cash, cash equivalents and short-term investments as of December 31, 2023, together with these amounts results in a pro-forma December 31, 2023 cash balance of approximately $104 million
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In addition, Atara expects to achieve $40 million of the $100 million in total potential regulatory milestones by BLA acceptance
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Atara expects to receive $20 million of these regulatory milestones in April based on the recent positive pre-BLA meeting, another $20 million in connection with BLA acceptance, and the remaining $60 million in potential regulatory milestones in connection with BLA approval
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Atara expects full year 2024 operating expenses to decrease by approximately 35% year-over-year, with the large majority of the reduction beginning in Q2 2024 and continuing for the remainder of the year
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Atara expects that cash, cash equivalents and short-term investments as of December 31, 2023, plus the proceeds received in Q1 2024 as outlined above from:
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Closing of the expanded global partnership with Pierre Fabre Laboratories;
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Issuance of pre-funded warrants; and

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The Company’s ATM program;
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When combined with certain anticipated payments from Pierre Fabre contingent upon the successful filing and approval of the tab-cel BLA, and operating efficiencies resulting from completed workforce reductions, and the planned transition of substantially all activities relating to tab-cel at the time of the BLA transfer to Pierre Fabre, in total will enable funding of planned operations into 2027

About ATA3219

ATA3219 combines the natural biology of unedited T cells with the benefits of an allogeneic therapy. It consists of allogeneic Epstein-Barr virus (EBV)-sensitized T cells that express a CD19 CAR construct for the treatment of CD19+ relapsed or refractory B-cell malignancies, including B-cell non-Hodgkin’s lymphoma and B-cell mediated autoimmune diseases including systemic lupus erythematosus (SLE) with kidney involvement (lupus nephritis [LN]). ATA3219 has been optimized to offer a potential best-in-class profile, featuring off-the-shelf availability. It incorporates multiple clinically validated technologies including a modified CD3ζ signaling domain (1XX) that optimizes expansion and mitigates exhaustion, enrichment during manufacturing for a less differentiated phenotype for robust expansion and persistence and retains the endogenous T-cell receptor without gene editing as a key survival signal for T cells contributing to persistence.

About ATA3431

ATA3431 is an allogeneic, bispecific CAR directed against CD20 and CD19, built on Atara’s EBV T-cell platform. The design consists of a tandem CD20-CD19 design, with binders oriented to optimize potency. Dual targets address the limitations of single antigen loss and tumor variability. ATA3431 features a novel 1XX costimulatory domain, memory phenotype, and retained, unedited T-cell receptor. Preclinical data have demonstrated early evidence of antitumor activity, long-term persistence, and superior tumor growth inhibition compared to an autologous CD19/CD20 CAR T benchmark.

Next-Generation Allogeneic CAR T Approach

Atara is focused on applying Epstein-Barr virus (EBV) T-cell biology, featuring experience in over 600 patients treated with allogeneic EBV T cells, and novel chimeric antigen receptor (CAR) technologies to meet the current limitations of autologous and allogeneic CAR therapies head-on by advancing a potential best-in-class CAR T pipeline in oncology and autoimmune disease. Unlike gene-edited approaches aimed at inactivating T-cell receptor (TCR) function to reduce the risk for graft-vs-host disease, Atara’s allogeneic platform maintains expression of the native EBV TCR that promote in vivo functional persistence while also demonstrating inherently low alloreactivity due to their recognition of defined viral antigens and partial human leukocyte antigen (HLA) matching. A molecular toolkit of clinically-validated technologies—including the 1XX costimulatory domain designed for better cell fitness and less exhaustion while maintaining stemness—offers a differentiated approach to addressing significant unmet need with the next generation CAR T.