On January 8, 2024 BioCryst Pharmaceuticals, Inc. (Nasdaq: BCRX) reported preliminary, unaudited ORLADEYO (berotralstat) net revenue for the fourth quarter and full year 2023 (Press release, BioCryst Pharmaceuticals, JAN 8, 2024, View Source [SID1234639058]). The company also provided guidance for full year 2024 ORLADEYO net revenue, full year 2024 operating expenses, expected peak ORLADEYO sales and an accelerated path to profitability.

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"After three years on the market, ORLADEYO continues on a steady growth trajectory to achieve $1 billion at peak. This commercial success, alongside our proven discovery platform that is producing additional first-in-class or best-in-class molecules, uniquely positions BioCryst to achieve financial independence from the capital markets and accelerate our path to profitability," said Jon Stonehouse, president and chief executive officer of BioCryst.

The company also announced that, if its ongoing proof-of-concept trial produces best-in-class data, it plans to out-license late-stage development and commercialization of BCX10013, its potential once-daily, oral Factor D inhibitor, to a partner that can drive the speed and breadth of investment required to accelerate BCX10013 for patients across multiple complement-mediated diseases and maximize the commercial potential of the program. As a result, the company has reduced the size of its R&D organization and accelerated its timeline to profitability.

Preliminary Fourth Quarter and Full Year 2023 ORLADEYO Revenue and 2024 ORLADEYO Outlook
Preliminary, unaudited ORLADEYO net revenue in the fourth quarter of 2023 was $89.9 million (+27 percent y-o-y). Preliminary, unaudited ORLADEYO net revenue for full year 2023 was $325 million (+29 percent y-o-y).

The company expects full year 2024 global net ORLADEYO revenue to be between $380 million and $400 million. The general pattern of revenue throughout 2024 is expected to be similar to past years, with the seasonal impact of prescription reauthorizations and the potential impact of the Inflation Reduction Act in the first quarter driving a quarter-over-quarter revenue decline in the first quarter, followed by a strong return to growth in the second quarter.

"ORLADEYO growth remained strong in the fourth quarter of 2023 as hereditary angioedema patients gain the excellent attack control they expect. Comparing U.S. patient trends year over year (y-o-y), we had more new patient prescriptions and a lower average rate of monthly discontinuations in 2023 compared to 2022. U.S. performance combined with continued global expansion keep ORLADEYO on track for $1 billion in peak sales," said Charlie Gayer, chief commercial officer of BioCryst.

Operating Expense and Profitability Outlook
The company expects full year 2024 operating expenses to be between $365 million and $375 million, flat to expected full year 2023 operating expenses. The company now expects that R&D expenses in 2024 will be reduced by $20 million versus 2023. This represents a $45 million to $55 million reduction from the 2024 R&D expense guidance it provided at its R&D Day in November 2023, and reflects both the R&D restructuring and the postponement of previously planned capital expenditures at its Discovery Center in Alabama. SG&A expenses are expected to increase by $20 million in 2024, primarily to support the continued U.S. and global growth of ORLADEYO to $1 billion in peak sales.

This operating expense outlook does not reflect non-cash stock compensation expense, or one-time expenses related to the reduction of 59 jobs (10 percent of total organization) in the first quarter of 2024.

Based on the company’s disciplined approach to capital allocation, and the revenue expected from ORLADEYO, the company expects to achieve a full-year operating profit in 2024 (not including non-cash stock compensation), be approaching quarterly positive earnings per share (EPS) and positive cash flow in the second half of 2025 (not including non-cash stock compensation), and be profitable on an EPS basis, with positive cash flow, for full year 2026. The company expects it can achieve these financial milestones without raising additional funds and does not intend to draw the additional $150 million of debt available to it from Pharmakon.

Presentation Tuesday at 42nd Annual J.P. Morgan Healthcare Conference
On Tuesday, January 9, 2024 at 6:00 p.m. ET, the company will present at the 42nd Annual J.P. Morgan Healthcare Conference in San Francisco. Links to a live audio webcast and replay of the presentation may be accessed in the Investors section of BioCryst’s website at https://www.biocryst.com/.

On January 8, 2023 Beam Therapeutics presented its corporate presentation (Presentation, Beam Therapeutics, JAN 8, 2024, View Source [SID1234639057]).

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On January 8, 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 that it has entered into a definitive agreement for the issuance and sale of pre-funded warrants to purchase 27,272,727 shares of its common stock at a purchase price of $0.55 per pre-funded warrant share in a registered direct offering to entities affiliated with an existing institutional investor (Press release, Atara Biotherapeutics, JAN 8, 2024, View Source [SID1234639056]). The pre-funded warrants will have an exercise price of $0.0001 per share, and will be immediately exercisable upon issuance. The offering is expected to close on or about January 10, 2024, subject to the satisfaction of customary closing conditions.

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The gross proceeds to Atara from the offering are expected to be $15 million, before deducting estimated offering expenses payable by Atara. Atara currently intends to use the net proceeds from the offering for working capital and general corporate purposes.

The securities described above are being offered by Atara pursuant to a shelf registration statement on Form S-3 (No. 333-275256), including a base prospectus, that was previously filed by Atara with the U.S. Securities and Exchange Commission (the "SEC") and was declared effective on November 13, 2023. A prospectus supplement containing additional information relating to the offering will be filed with the SEC and will be available on the SEC’s website located at View Source

This press release shall not constitute an offer to sell or the solicitation of an offer to buy, 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 January 8, 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 Pascal Touchon, President and Chief Executive Officer of Atara, will present the Company’s 2023 accomplishments across strategic priorities and key upcoming milestones at the 42nd Annual J.P. Morgan Healthcare Conference on Thursday, January 11 at 9:45 a.m. PST / 12:45 p.m. EST (Press release, Atara Biotherapeutics, JAN 8, 2024, View Source [SID1234639055]).

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"Our off-the-shelf, allogeneic CAR EBV T cell pipeline now spans both oncology and autoimmune indications and is designed to overcome current limitations of autologous CAR T and other allogeneic cell therapy approaches. With preliminary clinical data expected later this year for ATA3219 in lymphoma and a planned IND in Lupus Nephritis in Q1, we enter 2024 with multiple opportunities for a potential best-in-class allogeneic product," said Pascal Touchon, President and Chief Executive Officer of Atara. "Meanwhile, we are encouraged by our latest pivotal study data for tab-cel supporting our plan to file a BLA in Q2 2024, while our global commercial partner Pierre Fabre is starting to prepare the U.S. launch."

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

Atara is advancing toward filing a Biologics License Application (BLA) in Q2 2024, which will include the latest pivotal ALLELE study data-cut that demonstrated a statistically significant 49% Objective Response Rate (ORR) (p<0.0001) and favorable safety profile consistent with previous analyses
This new data set augments the extensive database of pivotal and supportive data as part of the upcoming BLA filing package, collectively consisting of approximately 450 patients treated with tab-cel across multiple life-threatening diseases
The expanded global partnership with Pierre Fabre Laboratories for the U.S. and remaining global commercial markets for tab-cel closed on December 20, 2023
Under the agreement, Atara received approximately USD 27 million in cash upfront at the closing of the deal, with the potential to receive up to a total of USD 640 million in milestone payments, development funding, and significant double-digit tiered royalties on net sales
Tab-cel for Potential Indication Expansion

Positive new clinical data from a combined analysis, including the first reported data from the multicohort Phase 2 EBVision trial, were presented during an oral session at the ESMO (Free ESMO Whitepaper) Immuno-Oncology Annual Congress
In the pooled analysis, an ORR of 77.8% was observed in 18 central nervous system (CNS) EBV+ PTLD patients including 1 CNS EBV+ PTLD patient with no prior treatment, who achieved a complete response
One- and two-year overall survival rates were higher in responders (85.7% and 66.7%, respectively) versus non-responders (0% and 0%, respectively)
Tab-cel was well tolerated, with no reports of serious treatment-related fatal or life-threatening treatment-emergent adverse events (TEAEs), and no reports of serious treatment-related TEAEs of neurotoxicity, organ rejection, graft versus host disease, or tumor flare reaction of any grade
Enrollment is continuing at sites in the potential label expansion multi-cohort Phase 2 EBVision trial evaluating new patient populations, including 1L EBV+ PTLD and EBV+ immunodeficiency-associated lymphoproliferative diseases (IA-LPDs)
CAR-T Programs (Hematological Malignancies and Autoimmune Conditions)

ATA3219

Atara is progressing development of ATA3219, an allogeneic, off-the-shelf CAR T targeting CD19, optimized for a memory phenotype and incorporating a next generation 1XX signaling domain
Pre-clinical data support a potential best-in-class profile with longer persistence and superior anti-tumor efficacy compared to an autologous CD19 CAR T benchmark
Site selection and activation is ongoing for the Phase 1 study in relapsed/refractory B-cell non-Hodgkin’s lymphoma (NHL) and progressing toward enrolling the first patient in Q1 2024
Preliminary clinical data in lymphoma anticipated H2 2024
Planned Q1 2024 IND submission in Lupus Nephritis following compelling clinical results from autologous CD19 CAR T academic clinical study showing 8/8 patients attaining remission1
Atara’s EBV CAR T cells may offer a differentiated therapeutic approach—off-the-shelf accessibility, no requirement for gene editing, and a less differentiated phenotype driving cellular fitness—with the potential for rapid and deep B-cell depletion
ATA3219 autoimmune development is building upon the favorable safety profile of Atara’s allogeneic EBV T cells in autoimmune disease
ATA3431

Positive preclinical data presented at ASH (Free ASH Whitepaper) for ATA3431, an allogeneic, dual-targeted CAR directed against CD20 and CD19 to mitigate CD19 antigen escape, built on Atara’s EBV T-cell platform with novel 1XX stimulation for enhanced persistence
Data showed superior in vivo anti-tumor activity, survival, and functional persistence of ATA3431 compared to an autologous CD20- CD19 CAR-T benchmark
Atara is advancing ATA3431 into IND-enabling studies
Strategic Restructure and Financial Impact

Atara is undertaking a strategic restructuring and reducing its current workforce of 225 by approximately 25% reflecting its evolving corporate strategy and pipeline focus to progress its potential best-in-class allogeneic CAR-T portfolio for cancer and autoimmune diseases
Atara will focus on executing its remaining responsibilities under the tab-cel collaboration with Pierre Fabre Laboratories, including filing the BLA in Q2 2024, and advancing its differentiated allogeneic CAR-T (AlloCAR-T) ATA3219 and ATA3431 programs to key milestones in 2024
The strategic restructuring, combined with anticipated payments upon successful filing and approval of tab-cel BLA from our expanded global partnership, and the Company’s existing cash, cash equivalents and short-term investments as of September 30, 2023, is expected to fund the Company’s planned operations into 2027
A live audio webcast of the presentation will be available by visiting the Investors & Media – News & Events section of atarabio.com on Thursday, January 11, at 9:45 a.m. PST / 12:45 p.m. EST. An archived replay of the webcast will be available on the Company’s website for 30 days following the live presentation. A new corporate presentation will be available on Monday, January 8 at 8:00 a.m. EST / 5:00 a.m. PST.

Next-Generation Allogeneic CAR-T Approach

Atara is focused on applying Epstein-Barr virus (EBV) T-cell biology, featuring experience in over 500 patients treated, 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, EBV T cells maintain expression of native TCRs 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.

On January 8, 2024 Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, "Astellas") reported the U.S. Food and Drug Administration (FDA) issued a complete response letter on January 4, 2024, regarding the Biologics License Application (BLA) for zolbetuximab, an investigational agent for the treatment of patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive (Press release, Astellas, JAN 8, 2024, View Source [SID1234639054]).

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The FDA stated that the agency cannot approve the BLA by the Prescription Drug User Fee Act (PDUFA) action date of January 12, 2024, due to unresolved deficiencies following its pre-license inspection of a third-party manufacturing facility for zolbetuximab. The FDA has not raised any concerns related to the clinical data, including efficacy or safety, of zolbetuximab, and is not requesting additional clinical studies. Astellas is working closely with the FDA and the third-party manufacturer to establish a timeline to quickly resolve the agency’s feedback. No other Astellas products are affected.

Moitreyee Chatterjee-Kishore, Ph.D., M.B.A., Senior Vice President and Head of Immuno-Oncology Development, Astellas
"We remain confident in zolbetuximab’s clinical profile and potential to fill a significant therapeutic gap for those diagnosed with advanced gastric or GEJ cancer whose tumors are CLDN18.2 positive. Astellas is committed to working with the FDA and the third-party manufacturer to address the agency’s feedback, and to bringing zolbetuximab to U.S. patients in need, as soon as possible."

Regulatory applications for zolbetuximab are also under review in several other countries and regions, including Japan, Europe, and China.

The impact of this matter on Astellas’ financial results in the fiscal year ending March 31, 2024, will be limited.

For more information, please see the press release "Astellas Announces U.S. FDA Grants Priority Review for Zolbetuximab Biologics License Application" issued on July 6, 2023.

About Zolbetuximab
Zolbetuximab is an investigational, first-in-class chimeric IgG1 monoclonal antibody (mAb) that targets and binds to claudin 18.2 (CLDN18.2), a transmembrane protein. Zolbetuximab acts by binding to CLDN18.2 on the cancer cell surface of gastric epithelial cells. In pre-clinical studies, this binding interaction then induces cancer cell death by activating two distinct immune system pathways — antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).1 Zolbetuximab has not been approved by any regulatory bodies for the treatment of patients with gastric and GEJ cancers, and there is no guarantee the agent will receive regulatory approval or become commercially available for the uses being investigated.