On February 28, 2023 Avidity Biosciences, Inc. (Nasdaq: RNA), a biopharmaceutical company committed to delivering a new class of RNA therapeutics called Antibody Oligonucleotide Conjugates (AOCs), reported financial results for the fourth quarter and year ended December 31, 2022 and highlighted recent corporate progress (Press release, Avidity Biosciences, FEB 28, 2023, View Source [SID1234627889]).

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"In 2022, we executed on our goal of advancing three rare disease programs into clinical development and demonstrated the first-ever successful targeted delivery of RNA into muscle, a revolutionary advancement for the field of RNA therapeutics," said Sarah Boyce, president and chief executive officer at Avidity. "Building on our AOC proof of platform data, 2023 will be another important year for Avidity. We look forward to Phase 1/2 MARINA and MARINA-OLE data as well as results from healthy volunteers in the Phase 1/2 EXPLORE44 trial while continuing to expand the broad utility of our AOC platform."

"We are in a strong financial position with more than $600 million at year-end reflecting approximately $224M in net proceeds from our successful financing in December. We are well funded into mid-2025 as we advance our clinical development programs for AOC 1001, AOC 1044 and AOC 1020, as well as expand our AOC platform and pipeline programs including our recently announced internal programs in skeletal muscle and cardiology" said Mike MacLean, chief financial officer and chief business officer at Avidity.
Clinical Development Programs – Achievements & Updates
AOC 1001
•Positive interim data from the preliminary assessment of AOC 1001 in the Phase 1/2 MARINA study demonstrated first-ever successful targeted delivery of RNA to skeletal muscle, DMPK reduction, splicing improvements and early signs of clinical activity with improvement in myotonia in some participants.
•Top-line data from the MARINA trial is anticipated in 2023 and preliminary data from the MARINA-OLE trial is anticipated in late 2023.
•The company plans to give an update on the AOC 1001 partial clinical hold at the end of the first quarter in 2023.

AOC 1044
•The FDA cleared Avidity to proceed with the Phase 1/2 EXPLORE44 clinical trial of AOC 1044 for the treatment of DMD mutations amenable to exon 44 skipping (DMD44). AOC 1044 is the first of multiple AOCs being developed for DMD and is the first AOC PMO to advance into the clinic.
◦The EXPLORE44 trial is a randomized, placebo-controlled, double-blind, Phase 1/2 clinical trial to evaluate AOC 1044 in approximately 40 healthy volunteers and 24 participants with DMD44, ages seven to 27 years old.

•Data from healthy volunteers in the EXPLORE44 trial is anticipated in the second half of 2023.

AOC 1020
•The FDA cleared Avidity to proceed with the Phase 1/2 FORTITUDE clinical trial of AOC 1020 in adults with facioscapulohumeral muscular dystrophy (FSHD).
◦The FORTITUDE trial is a randomized, placebo-controlled, double-blind, Phase 1/2 clinical trial designed to evaluate AOC 1020 in approximately 70 adult participants with FSHD.
◦The FDA granted AOC 1020 Fast Track Designation in January 2023.
◦The FDA and the European Medicines Agency (EMA) granted AOC 1020 Orphan Designation in February 2023.
•Data from a preliminary assessment in approximately half of participants in the FORTITUDE trial is anticipated in the first half of 2024.

Pipeline Advancements
•Avidity announced that it advanced and expanded its wholly-owned early stage AOC pipeline including adding a rare cardiac program and an additional program in rare skeletal muscle disease.

Organizational Highlights
•The company announced in February that Arthur A. Levin, Ph.D., joined its board of directors and transitioned to distinguished scientist and strategic leader at Avidity.
•W. Michael Flanagan, Ph.D. was promoted in February to chief scientific and technical officer.
Fourth Quarter and Year-End 2022 Financial Results
•Cash, Cash Equivalents and Marketable Securities: Cash, cash equivalents and marketable securities totaled $610.7 million as of December 31, 2022, which reflects $344.6 million raised in 2022, inclusive of $223.8 million of net proceeds from our follow-on financing. In addition, subsequent to December 31, 2022, we have raised $22.3 million through our "at the market" program.

•Collaboration Revenue: Collaboration revenue, including reimbursable expenses, primarily relates to Avidity’s partnership with Eli Lilly and Company (Lilly) and totaled $2.7 million for the fourth quarter of 2022 compared with $1.9 million for the fourth quarter of 2021, and $9.2 million for the full year 2022 compared with $9.3 million for the full year 2021.
•Research and Development (R&D) Expenses: R&D expenses include external and internal costs associated with research and development activities. These expenses were $45.6 million for the fourth quarter of 2022 compared with $33.0 million for the fourth quarter of 2021, and $150.4 million for the full year 2022 compared with $101.2 million for the full year 2021. The increases were primarily driven by the advancement of AOC 1001,

AOC 1020 and AOC 1044, as well as internal and external costs related to the expansion of the company’s overall research capabilities.
•General and Administrative (G&A) Expenses: G&A expenses primarily consist of employee-related expenses, professional fees, insurance costs and patent filing and maintenance fees. These expenses were $10.4 million for the fourth quarter of 2022 compared with $7.4 million for the fourth quarter of 2021, and $37.7 million for the full year 2022 compared with $26.2 million for the full year 2021. The increases were primarily due to higher personnel costs and professional fees to support the company’s expanded operations.

On February 28, 2023 Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) products for cancer, reported a corporate update and reported financial results for the quarter and year ended December 31, 2022 (Press release, Allogene, FEB 28, 2023, View Source [SID1234627888]).

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"We are very proud that data from our pipeline candidates continues to break new ground in the field of allogeneic cell therapy. From our CD19 program for non-Hodgkin lymphoma to our BCMA program for multiple myeloma, we have established that our AlloCAR T technology can induce deep, clinically meaningful responses in patients," said David Chang, M.D., Ph.D., President, Chief Executive Officer and Co-Founder of Allogene. "We continue to hear from physicians that gaining access to autologous CAR T therapy and the inevitable wait times associated with manufacturing remain a critical factor for patients. We believe the future of CAR T rests on the ability for an off-the-shelf option to address both time and access. The data we presented at our R&D Showcase in late 2022 indicates Allogene is making large strides toward giving patients back precious time."

Pipeline Updates

ALLO-501A: Anti-CD19 AlloCAR T Program
In October 2022, Allogene initiated the industry’s first potentially pivotal Phase 2 allogeneic CAR T clinical trial with ALLO-501A. The single-arm trial is enrolling patients with relapsed/refractory (r/r) large B cell lymphoma (LBCL) and utilizes a single dose of ALLO-501A (120 million CAR+ cells) with the FCA90 (fludarabine, 30mg/m2, cyclophosphamide 300 mg/m2 and ALLO-647 30 mg, daily for 3 days) lymphodepletion regimen. The ALPHA2 trial will enroll approximately 100 patients who have received at least two prior lines of therapy and have not received prior anti-CD19 therapy. The primary endpoint of this trial is overall response rate (ORR), and the key secondary endpoint is duration of response (DoR). Patients may receive treatment as an outpatient at the investigator’s discretion. The Company expects to complete enrollment in the Phase 2 ALPHA2 trial in 1H 2024.

In November 2022, Phase 1 data from the ALPHA trial with ALLO-501 and ALPHA2 trial with ALLO-501A for the treatment of r/r LBCL was presented at the Company’s R&D Showcase. Data from the Phase 1 trials of ALLO-501 and ALLO-501A support the ability of a single administration of CAR T cells to generate deep and durable responses comparable to those with approved autologous CAR T therapies. Highlights included:

As of the October 25, 2022 data cutoff, the ORR and Complete Response (CR) rate was 67% and 58%, respectively, among the 12 patients treated with the Single Dose FCA90 regimen using Alloy process material. The median duration of response was 23.1 months.
Of patients who received single dose FCA90 and evaluable at six months, the ongoing CR rate was 50% and all CRs at six months were durable at 12 months. The longest CR ongoing at 26+ months.
Phase 1 trials demonstrated a manageable safety profile with no observed dose limiting toxicities (DLTs), graft-vs-host disease (GvHD) or severe immune effector cell-associated neurotoxicity syndrome (ICANS).
Among patients treated with Single Dose FCA90, there was no Grade 3+ cytokine release syndrome (CRS). One patient (8%) experienced a Grade 3+ infection and two (17%) experienced prolonged Grade 3+ cytopenia.
92% of all enrolled patients received product with 100% of infused product manufactured and released per product specifications. Patients were able to initiate treatment within two days of enrollment.
The Company is preparing for a Phase 3 study in earlier line LBCL targeting trial initiation in 1H 2024.

The Company is developing ALLO-647, its proprietary anti-CD52 monoclonal antibody intended to enable expansion and persistence of AlloCAR T product candidates, including ALLO-501A. The EXPAND trial, which is intended to demonstrate the contribution of ALLO-647 to the lymphodepletion regimen, will be open to enrollment early in the second quarter.

ALLO-715: Anti-BCMA AlloCAR T Programs
Data from the Phase 1 UNIVERSAL trial with ALLO-715 for the treatment of r/r multiple myeloma (MM) was also presented at the Company’s R&D Showcase and subsequently published in Nature Medicine, accompanied by an editorial. The UNIVERSAL trial is the first allogeneic anti-BCMA CAR T to demonstrate proof-of-concept in MM with response rates that are similar to an approved autologous CAR T therapy. Highlights include:

Dose expansion cohorts demonstrated substantial and durable responses.
Through a median follow-up of 14.8 months as of the October 11, 2022 data cutoff, the ORR was 67% in the FCA60 cohort and the very good partial response or better rate (VGPR+) was 42%. All VGPR+ were minimal residual disease (MRD) negative.
The median DoR was 9.2 months, with the longest response ongoing at 24 months.
92% of all enrolled patients received product with 100% of infused product manufactured and released as per product specifications. None of the patients received bridging therapy and patients were able to initiate treatment immediately following enrollment. Median time from enrollment to lymphodepletion was 5 days.
Safety profile was manageable with low-grade and reversible neurotoxicity and no GvHD. Eight patients (29%) experienced Grade 3+ infections and eight patients experienced prolonged Grade 3+ cytopenias.
The Company is evaluating manufacturing processes improvements across its BCMA candidates to achieve optimal performance.

ALLO-316: Anti-CD70 AlloCAR T Program
ALLO-316, the Company’s first AlloCAR T candidate for solid tumors, targets CD70, an antigen expressed on clear cell renal cell carcinoma (RCC) and other malignancies. At the Company’s R&D Showcase, the Company presented initial data demonstrating promising anti-cancer activity in the subset of nine patients with confirmed CD70-positive RCC from the ongoing Phase 1 TRAVERSE trial. Highlights include:

As of the data cutoff date of November 17, 2022, the disease control rate (DCR) in patients who were CD70+ was 100% including three patients who achieved a partial response (PR) (two confirmed and one unconfirmed with the longest response lasting until month eight).
Cell expansion in patients with CD70 positive tumor was robust, and there was a trend toward greater tumor shrinkage in patients with high CD70 expression.
Across all patients treated in the trial, ALLO-316 has demonstrated a generally manageable safety profile with no GvHD. One dose limiting toxicity of auto-immune hepatitis occurred in the second dose level. Grade 3+ prolonged cytopenia was observed in three patients (18%). Grade 3 CRS was observed in one patient. Neurotoxicity was low grade, reversible and seen in only three patients (18%).
The Company is deploying a new investigational in vitro companion diagnostic (IVD) assay designed to prospectively assess CD70 expression levels to enhance patient selection. TRAVERSE will continue to explore varying cell dose and lymphodepletion regimens, including FC and FCA. Subject to ongoing results in the TRAVERSE trial, the Company intends to complete planned dose exploration and initiate expansion cohort enrollment in 2023. The Company may also investigate ALLO-316 for other CD70 expressing solid tumors and hematologic indications, or in combination with other anticancer therapies such as immune checkpoint inhibitors.

Next Generation Platform Technology
Allogene has pursued an integrated strategy within Research and Development aimed at matching technology with insights obtained from the clinic to create solutions designed to advance patient outcomes. One of these is Dagger, a proprietary technology designed to control rejection of AlloCAR T cells by the host immune cells. This technology deploys a CD70 CAR on AlloCAR T cells in an effort to recognize and deplete CD70 positive alloreactive host T cells. Preclinical data indicate that CD70 Dagger CARs can be combined with other anti-tumor CARs in a single cell, providing both protection from allorejection and dual specificity killing capability, thus offering a differentiated next generation product candidate profile.

Fourth Quarter and Year-End Financial Results

Research and development expenses were $75.4 million for the fourth quarter of 2022, which includes $7.4 million of non-cash stock-based compensation expense. For the full year of 2022, research and development expenses were $256.4 million. Research and development expense for the year includes $42.5 million of non-cash stock-based compensation expense.
General and administrative expenses were $21.0 million for the fourth quarter of 2022, which includes $9.8 million of non-cash stock-based compensation expense. For the full year of 2022, general and administrative expenses were $79.3 million, which includes $41.1 million of non-cash stock-based compensation expense.
Net loss for the fourth quarter of 2022 was $94.8 million, or $0.66 per share, including non-cash stock-based compensation expense of $17.2 million. For the full year of 2022, net loss was $332.6 million, or $2.32 per share, including non-cash stock-based compensation expense of $83.6 million.
The Company had $576.5 million in cash, cash equivalents, and investments as of December 31, 2022.
2023 Financial Guidance

The Company expects a decrease in cash, cash equivalents, and investments of approximately $250 million in 2023. Based on current expectation, the Company expects the cash runway to be sufficient to fund operations into 2025. GAAP Operating Expenses are expected to be approximately $350 million, including estimated non-cash stock-based compensation expense of approximately $90 million. These estimates exclude any impact from potential business development activities.
Conference Call and Webcast Details
Allogene will host a live conference call and webcast today at 2:00 p.m. Pacific Time / 5:00 p.m. Eastern Time to discuss financial results and provide a business update. If you would like the option to ask a question on the conference call, please use this link to register. Upon registering for the conference call, you will receive a personal PIN to access the call, which will identify you as the participant and allow you the option to ask a question. The listen-only webcast will be made available on the Company’s website at www.allogene.com under the Investors tab in the News and Events section. Following the live audio webcast, a replay will be available on the Company’s website for approximately 30 days.

On February 28, 2023 United Therapeutics Corporation (Nasdaq: UTHR), a public benefit corporation, announced today that Michael Benkowitz, President and Chief Operating Officer, reported that it will provide an overview and update on the company’s business during a fireside chat session at the Cowen 43rd Annual Health Care Conference in Boston (Press release, United Therapeutics, FEB 28, 2023, View Source [SID1234627886]).

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The session will take place on Tuesday, March 7, 2023, from 9:10 a.m. to 9:40 a.m., Eastern Standard Time, and can be accessed via a live webcast on the United Therapeutics website at View Source An archived, recorded version of the session will be available approximately 24 hours after the session ends and can be accessed at the same location for 90 days.

On February 28, 2023 Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel therapies for serious rare and ultrarare genetic diseases, reported that Emil D. Kakkis, M.D., Ph.D., the company’s chief executive officer and president, will participate in an Orphan Neuro Panel at Cowen’s 43rd Annual Health Care Conference on Tuesday, March 7, 2023, at 10:30 a.m. ET (Press release, Ultragenyx Pharmaceutical, FEB 28, 2023, View Source [SID1234627885]).

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The live and archived webcast of the panel will be accessible from the company’s website at View Source The replay of the webcast will be available for 30 days.

On February 28, 2023 Tvardi Therapeutics, Inc. ("Tvardi"), a privately held, clinical-stage biopharmaceutical company focused on the development of STAT3 inhibitors, reportedthat the company has been invited to participate at the Cowen 43rd Annual Health Care Conference (Press release, Tvardi Therapeutics, FEB 28, 2023, View Source [SID1234627884]). The management team will hold one-on-one meetings on March 8, 2023, to review emerging clinical data.

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Cowen’s 43rd Annual Health Care Conference is taking place March 6 – 8, 2023, at the Boston Marriott Copley Place in Boston, MA. The conference incorporates presentations, fireside chats and innovative panel discussions hosted by members of the Cowen research team that focus on various aspects of the healthcare industry.