On May 9, 2024 HOOKIPA Pharma Inc. (NASDAQ: HOOK, ‘HOOKIPA’), a company developing a new class of immunotherapeutics based on its proprietary arenavirus platform, reported financial results and recent business highlights for the first quarter of 2024 (Press release, Hookipa Biotech, MAY 9, 2024, View Source [SID1234642992]).

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"The first quarter was about focus at HOOKIPA. We are embarking on a pivotal trial for HB-200 in combination with pembrolizumab and made important decisions to align our organization for late-stage clinical trial execution. We also added to the depth of our executive team with a new Chief Development Officer, Mark Winderlich, who brings crucial experience to help us execute on our clinical development strategy," said Joern Aldag, Chief Executive Officer of HOOKIPA. "We have made great progress and have an FDA-aligned pivotal Phase 2/3 trial design that is patient-centric and we believe has a high probability of success. Our path forward is clear, and the team is excited to take a major step on our path to deliver better outcomes for patients."

Business Highlights and Recent Developments

Oncology

HOOKIPA is preparing to start a seamless pivotal Phase 2/3 trial of HB-200 in combination with pembrolizumab for the treatment of patients with Human Papillomavirus 16-positive (HPV16+) recurrent/metastatic PD-L1 CPS ≥ 20 oropharyngeal squamous cell carcinoma (OPSCC) in the first line setting.
The Phase 2/3 trial design and protocol are based on alignment with the FDA following the Company’s Type C meeting.
EMA granted PRIME designation to the investigational product HB-200 in combination with pembrolizumab. PRIME designation is intended to expedite development and review of drug candidates, alone or in combination with other drugs. Eligibility and approval are based on preliminary clinical evidence and indicate that the drug candidate may offer substantial improvement over existing therapies.
The Company anticipates the first patient will be enrolled in the fourth quarter of 2024. HB-200 was accepted for an oral abstract presentation at the ASCO (Free ASCO Whitepaper) 2024 Annual Meeting with data from approximately 40 patients treated with HB-200 in combination with pembrolizumab.
The HB-700 program is a novel arenaviral immunotherapy for KRAS-mutated cancers, including the five mutations that are the primary causes of lung, pancreatic and colon cancers. The Company received clearance from the U.S. Food and Drug Administration (FDA) for its Investigational New Drug (IND) application for HB-700 for the treatment of KRAS-mutated cancers. Effective April 25, 2024, HOOKIPA regained full control of the associated intellectual property portfolio and has full collaboration and licensing rights for this program.
Infectious Disease

HB-400 is currently being evaluated in a Phase 1 trial and is one of two independent development programs in HOOKIPA’s collaboration and license agreement with Gilead Sciences, Inc. (Gilead). Gilead is solely responsible for further development and commercialization of the HBV product candidate.
HB-500 is an investigational therapeutic vaccine for the treatment of human immunodeficiency virus (HIV), also partnered with Gilead. HOOKIPA received FDA clearance of its IND application in the fourth quarter of 2023 and expects to initiate a Phase 1 clinical trial of HB-500 in people with HIV in the second quarter of 2024. Under the collaboration agreement with Gilead, HOOKIPA is eligible for a milestone payment upon dosing the first patient in this trial.
Corporate and Financial Updates

Corporate Highlights

On January 29, 2024, HOOKIPA provided an update on its business priorities and oncology partnership programs. The Company announced that it will focus its resources in two strategic areas: (1) the clinical development of a randomized trial for its HB-200 program and (2) its two Gilead-partnered infectious disease cure programs for hepatitis B and HIV.
Mark Winderlich, Ph.D., joined the Company on April 1, 2024, as Chief Development Officer to lead HOOKIPA’s clinical research and development organization.
Financial Highlights

HOOKIPA received a final $10.0 million milestone payment under its now-terminated HB-700 collaboration agreement with Roche. The success-based milestone payment was achieved in connection with HOOKIPA’s submission of an IND application for HB-700 for the treatment of KRAS mutated tumors.
Total revenues of $36.6 million, mainly driven by the recognition of previously received upfront and milestone payments under the now-terminated Roche collaboration, as well as the recent HB-700 milestone achievement, led to a profitable first quarter of 2024.
Anticipated Catalysts & Milestones

Program Indication Upcoming Anticipated Catalysts
Oncology Programs
HB-200 HPV16+ HNSCC
Additional Phase 2 first-line data for HB-200 in combination with pembrolizumab (ASCO 2024)
Pivotal study start (4Q 2024)
HB-700 KRAS
Publication of preclinical data (ASCO 2024)

Infectious Disease Programs: Gilead-Partnered
HB-400 HBV
Gilead-led: Phase 1b actively enrolling
Next milestone: Initiation of Phase 2
(timing determined by Gilead)
HB-500 HIV
Initiation of Phase 1 trial; first patient dosed and associated milestone payment (2Q 2024)

First Quarter 2024 Financial Results

Cash Position: HOOKIPA’s cash, cash equivalents and restricted cash as of March 31, 2024 was $93.0 million compared to $117.5 million as of December 31, 2023. The decrease was primarily attributable to cash used in operating activities.

Revenue: Revenue was $36.6 million for the three months ended March 31, 2024, compared to $3.2 million for the same period in 2023. The increase was primarily due to higher partial revenue recognition under the Roche collaboration as a result of the termination of the agreement, leading to accelerated recognition of the upfront and milestone payments that were initially recorded as deferred revenue.

Research and Development Expenses: HOOKIPA’s research and development expenses were $20.2 million for the three months ended March 31, 2024, compared to $20.9 million for the same period in 2023. The primary drivers of the decrease in research and development expenses were lower personnel-related and laboratory-related expenses, partially offset by higher clinical study expenses for the HB-200 program.

General and Administrative Expenses: General and administrative expenses amounted to $4.1 million for the three months ended March 31, 2024, compared to $4.9 million for the same period in 2023. The primary driver of the decrease in general and administrative expenses was a decrease in personnel-related expenses.

Restructuring Expenses: Restructuring expenses amounted to $1.3 million for the three months ended March 31, 2024, and resulted from severance and other personnel costs as well as consulting costs associated with the Company’s restructuring plan announced in January 2024.

Net Income (Loss): HOOKIPA’s net income was $14.4 million for the three months ended March 31, 2024, compared to a net loss of $19.7 million for the same period in 2023. This increase was primarily due to the accelerated recognition of upfront and milestone payments under the Roche collaboration.

On May 9, 2024 Monte Rosa Therapeutics, Inc. (Nasdaq: GLUE), a clinical-stage biotechnology company developing novel molecular glue degrader (MGD)-based medicines, reported business highlights and financial results for the first quarter ending March 31, 2024 (Press release, Monte Rosa Therapeutics, MAY 9, 2024, View Source [SID1234643008]).

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"We’re excited by the significant advances made across our entire portfolio, including both our oncology and immunology/inflammation programs," said Markus Warmuth, M.D., Chief Executive Officer of Monte Rosa Therapeutics. "Our Phase 1/2 clinical trial evaluating MRT-2359 for MYC-driven solid tumors is on track and we plan to announce the recommended Phase 2 dose later this quarter and to report clinical data from this program in the second half of the year. We eagerly anticipate the initiation of a Phase 1 study of MRT-6160, the first of our MGD drug candidates for immune-related diseases, in mid-2024, with results from the study expected in Q1 2025. Preclinical GLP toxicology data we’ve announced today, along with data in multiple disease models, suggest the potential for a highly differentiated profile across multiple autoimmune diseases. Additionally, MRT-8102, our NEK7-directed MGD targeting diseases driven by IL-1β and the NLRP3 inflammasome, is rapidly progressing toward clinical studies. We’ve recently demonstrated strong CNS exposure and NEK7 degradation in non-human primates, supporting the potential development of MRT-8102 in neurologic indications and obesity amongst others, in addition to its potential use in gout, pericarditis, and other peripheral inflammatory conditions. We’re also very pleased to announce our discovery program for CCNE1 (Cyclin E1), a well-validated oncology target generally considered undruggable by conventional modalities. We believe our ability to degrade CCNE1 potently and selectively and to elicit anti-tumor activity in in vivo models provides further validation for the differentiation of our QuEEN discovery engine and the potential of our MGDs against a broad spectrum of targets."

Dr. Warmuth concluded, "The rapid and efficient progression of our pipeline clearly illustrates the power of our AI/ML-driven QuEEN discovery engine. Through our ongoing internal efforts as well as our research collaboration with Roche, we look forward to continuing this strong progress."

RECENT HIGHLIGHTS

MRT-2359, GSPT1-directed MGD for MYC-driven solid tumors

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Monte Rosa continues to evaluate MRT-2359 in a Phase 1/2 clinical trial in MYC-driven solid tumors (NCT05546268). Enrollment is ongoing in backfill cohorts at clinically active doses using a 5-days-on, 9-days-off drug schedule and in dose escalation cohorts using a 21-days-on, 7-days-off drug schedule. The Company is on track to determine the recommended Phase 2 dose (RP2D) in Q2 2024 and report Phase 1 study results in H2 2024. Monte Rosa expects to initiate the Phase 2 portion of the study before year-end.
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The Company presented preclinical data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting demonstrating that treatment with MRT-2359 resulted in marked tumor regressions in the AR-V7- and c-MYC-expressing 22RV1 xenograft mouse model of prostate cancer associated with resistance to anti-androgen agents.
MRT-6160, VAV1-directed MGD for systemic and neurological autoimmune/inflammatory diseases

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The MRT-6160 program is on track for an anticipated Investigational New Drug (IND) submission to the U.S. Food and Drug Administration (FDA) in Q2 2024, and initiation of a Phase 1 single ascending dose/multiple ascending dose (SAD/MAD) study in mid-2024. Phase 1 results are anticipated in Q1 2025.
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The Company reported additional results from completed preclinical GLP toxicology studies of MRT-6160 in rats and non-human primates (NHPs). The data demonstrate a highly favorable safety profile with no significant changes in peripheral immune cell compartments.
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Monte Rosa expects to present additional preclinical data for MRT-6160 in models of autoimmune and inflammatory diseases at the upcoming Digestive Disease Week (DDW) and European Alliance of Associations for Rheumatology (EULAR) medical meetings.
MRT-8102, NEK7-directed MGD for inflammatory diseases driven by IL-1β and the NLRP3 inflammasome

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In March 2024, Monte Rosa announced the initiation of IND-enabling studies for MRT-8102, a first-in-class NEK7-directed MGD for the treatment of inflammatory diseases driven by interleukin-1β (IL-1β) and the NLRP3 inflammasome, critical elements of the inflammatory process. This is the first development candidate to be declared from the Company’s NEK7 development program.
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Monte Rosa reported that MRT-8102 has demonstrated highly favorable CNS exposure and degradation in a study in cynomolgus monkeys. The data support the potential for development of MRT-8102 in diseases including Parkinson’s disease, Alzheimer’s disease, and obesity. The Company is evaluating applications across multiple inflammatory disorders.
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Monte Rosa expects to submit an IND application for MRT-8102 in Q1 2025.
CCNE1-directed MGD program for CCNE1-amplified tumors

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Monte Rosa reported a new discovery program for CCNE1 (Cyclin E1)-directed MGDs for the treatment of CCNE1-amplified tumors. CCNE1, a key component of the cell cycle and a known driver of many cancers, is generally considered an undruggable target by conventional modalities.
Additional corporate updates

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In October 2023, Monte Rosa entered into a strategic collaboration and licensing agreement with Roche, a global healthcare leader, to discover and develop MGDs against targets in cancer and neurological diseases. The collaboration continues to advance research activities according to plan.
ANTICIPATED MILESTONES

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Announce the recommended Phase 2 dose for the MRT-2359 Phase 1/2 study in Q2 2024 and report Phase 1 clinical results in H2 2024. Initiate the Phase 2 portion of the study before year-end. The Company is evaluating Phase 2 expansion cohorts in high-prevalence c-MYC-driven tumors including hormone receptor-positive breast cancer and prostate cancer, as well as tumor types and patient populations driven by L- and N-MYC including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and solid tumors with amplifications of L- and N-MYC.
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Submit an IND application for MRT-6160 in Q2 2024 and initiate a Phase 1 SAD/MAD study in healthy volunteers in mid-2024; report results from the Phase 1 study in Q1 2025. Monte Rosa expects to subsequently initiate proof-of-concept (POC) studies in autoimmune/inflammatory diseases including ulcerative colitis and rheumatoid arthritis, with additional potential POC studies in dermatology, rheumatology, and neurology indications.
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Submit an IND application for MRT-8102 in Q1 2025.
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Nominate a development candidate for the CDK2 preclinical program in 2024.

UPCOMING PRESENTATIONS

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Monte Rosa plans to present a poster at the Digestive Disease Week (DDW) Conference on May 21, 2024, in Washington, DC, titled, "MRT-6160, a VAV1-Directed Molecular Glue Degrader, Inhibits Disease Progression in a T-cell Transfer Mediated Murine Colitis Model Concomitant with Reduced Calprotectin Expression."
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Monte Rosa plans to present a poster at the European Alliance of Associations for Rheumatology (EULAR) Conference on June 14, 2024, in Vienna, Austria, titled, "MRT-6160, a VAV1-Directed Molecular Glue Degrader, Reduces Joint Inflammation, Cytokine Production, and Autoantibody Levels in a Collagen-Induced Arthritis Disease Model."

FIRST QUARTER 2024 FINANCIAL RESULTS

Collaboration Revenue: Collaboration revenue for the first quarter of 2024 was $1.1 million, compared with $0 during the same period in 2023. Collaboration revenue represents revenue recorded under the Roche License and Collaboration agreement.

Research and Development (R&D) Expenses: R&D expenses for the first quarter of 2024 were $27.0 million, compared to $26.8 million during the same period in 2023. R&D expenses were driven by the successful achievement of key milestones in our R&D organization, including the continuation of the MRT-2359 clinical study, the progression and growth of our preclinical pipeline, the preparation of MRT-6160 to enter the clinic, and the continued development of the Company’s QuEEN discovery engine. Non-cash stock-based compensation constituted $2.7 million of R&D expenses for Q1 2024, compared to $2.1 million in the same period in 2023.

General and Administrative (G&A) Expenses: G&A expenses for the first quarter of 2024 were $9.0 million compared to $7.5 million during the same period in 2023. The increase in G&A expenses was a result of increased headcount, stock-based compensation expense, and fees paid to consultants in order to support our growth and operations. G&A expenses included non-cash stock-based compensation of $2.2 million for the first quarter of 2024, compared to $1.8 million for the same period in 2022.

Net Loss: Net loss for the first quarter of 2024 was $32.0 million, compared to $33.3 million for the fourth quarter of 2023.

Cash Position and Financial Guidance: Cash, cash equivalents, restricted cash, and marketable securities as of March 31, 2024, were $197.8 million, compared to cash, cash equivalents, restricted cash, and marketable securities of $237.0 million as of December 31, 2023. The decrease of $39.2 million was primarily due to operational use of cash.

The Company expects its cash and cash equivalents to be sufficient to fund planned operations and capital expenditures into the first half of 2026.

About MRT-2359

MRT-2359 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader (MGD) that induces the interaction between the E3 ubiquitin ligase component cereblon and the translation termination factor GSPT1, leading to the targeted degradation of GSPT1 protein. The MYC transcription factors (c‑MYC, L-MYC and N-MYC) are well-established drivers of human cancers that maintain high levels of protein translation, which is critical for uncontrolled cell proliferation and tumor growth. Preclinical studies have shown this addiction to MYC-induced protein translation creates a dependency on GSPT1. By inducing degradation of GSPT1, MRT-2359 is designed to exploit this vulnerability, disrupting the protein synthesis machinery, leading to anti-tumor activity in MYC-driven tumors.

About MRT-6160

MRT-6160 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader of VAV1, which in our in vitro studies has shown deep degradation of its target with no detectable effects on other proteins. VAV1, a Rho-family guanine nucleotide exchange factor, is a key signaling protein downstream of both the T- and B-cell receptors. VAV1 expression is restricted to blood and immune cells, including T and B cells. Preclinical studies have shown that targeted degradation of VAV1 protein via an MGD modulates both T- and B-cell receptor-mediated activity. This modulation is evident both in vitro and in vivo, demonstrated by a significant decrease in cytokine secretion, proteins vital for maintaining autoimmune diseases. Moreover, VAV1-directed MGDs have shown promising activity in preclinical models of autoimmune diseases and thus have the potential to provide therapeutic benefits in multiple systemic and neurological autoimmune indications, such as multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, and dermatological disorders. Preclinical studies have demonstrated that MRT-6160 can inhibit disease progression in in vivo autoimmunity models.

About MRT-8102

MRT-8102 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader (MGD) that targets NEK7 for the treatment of inflammatory diseases driven by IL-1β and the NLRP3 inflammasome. NEK7 has been shown to be required for NLRP3 inflammasome assembly, activation and IL-1β release both in vitro and in vivo. Aberrant NLRP3 inflammasome activation and the subsequent release of active IL-1β and interleukin-18 (IL-18) has been implicated in multiple inflammatory disorders, including gout, cardiovascular disease, neurologic disorders including Parkinson’s disease and Alzheimer’s disease, ocular disease, diabetes, obesity, and liver disease. In a non-human primate model, MRT-8102 was shown to potently, selectively, and durably degrade NEK7, and resulted in near-complete reductions of IL-1β models following ex vivo stimulation of whole blood. MRT-8102 has shown a favorable profile in non-GLP toxicology studies.

On May 9, 2024 Phio Pharmaceuticals Corp. (Nasdaq: PHIO), a clinical stage biotechnology company whose proprietary INTASYL siRNA gene silencing technology is designed to make immune cells more effective in killing tumor cells, reported its Q1 2024 financial results and provided a business update (Press release, Phio Pharmaceuticals, MAY 9, 2024, View Source [SID1234643036]).

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Recent Corporate Updates

· Phio’s INTASYL compound PH-762 is currently being investigated in an open-label Phase 1b clinical study (NCT 06014086) to evaluate the safety and tolerability of intratumoral PH-762 in cutaneous squamous cell (cSCC), melanoma, or Merkel cell carcinoma. Two patients have already completed treatment. Four sites across the US are now engaged in the Phase 1b study. The sites are:
o George Washington University in Washington DC
o Banner MD Anderson in Arizona
o Centricity Research in Ohio
o Integrity Research in Florida.
· Presented new data on the immunotherapeutic activity of INTASYL at:
o 10th Annual Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Conference (ITOC10): this preclinical data demonstrates the potential of the INTASYL compound PH-905 targeting Cbl-b to improve the function of natural killer (NK) cells.
o 27th Annual American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper): this preclinical data demonstrates that intratumoral injection of PH-762 significantly inhibits tumor growth in murine cells and may generate memory-specific T cells.
· The INTASYL siRNA platform is the focus of a National Spotlight on PBS Viewpoint, a national program hosted by Dennis Quaid, and on Fox Business Network; both are airing through May.
· Patent granted by USPTO for two of its INTASYL Compounds, RXI-185 and RXI-231 that treat age-related skin disorders including photo-aging and dermal hyperpigmentation targeting down-regulation of the Matrix metalloproteinase-1(MMP-1) and Tyrosinase (TYR) proteins.

Financial Results

Cash Position

At March 31, 2024, we had cash of $6.5 million as compared with $8.5 million at December 31, 2023.

Research and Development Expenses

Research and development expenses were $1.1 million for the three months ended March 31, 2024 as compared with $2.1 million for the three months ended March 31, 2023, a decrease of 46%. The decrease was primarily driven by the Company’s cost rationalization measures in transitioning from a discovery research company to a product development company resulting in decreased costs for the wind-down of preclinical studies, salary-related costs and lab supplies. Additional decreases in research and development expenses were due to clinical consulting fees incurred in connection with the Company’s IND filing and manufacturing fees for PH-762 in the prior year period.

General and Administrative Expenses

General and administrative expenses were $1.1 million for the three months ended March 31, 2024 as compared with $1.5 million for the three months ended March 31, 2023, a decrease of 28%. The decrease was primarily due to decreases in consulting expenses and legal expenses as compared to the prior year period.

Net Loss

Net loss was $2.2 million for the three months ended March 31, 2024 as compared with $3.6 million for the three months ended March 31, 2023. The decrease in net loss was primarily due to the changes in research and development expenses, as described above.

On May 9, 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 first quarter 2024, recent business highlights, and key upcoming milestones for 2024 (Press release, Atara Biotherapeutics, MAY 9, 2024, View Source [SID1234642977]).

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"Our lead CAR T program, ATA3219, is advancing as a promising new therapeutic option for oncology and autoimmune diseases, where it is positioned to benefit from the unique characteristics of our proven allogeneic EBV T-cell platform," said Pascal Touchon, President and Chief Executive Officer of Atara. "This is anticipated to provide multiple near-term clinical milestones for ATA3219, including initial non-Hodgkin’s lymphoma data expected in the fourth quarter 2024, and initial lupus nephritis data in the first half of 2025, with plans to expand into a new SLE cohort without lymphodepletion. In addition, our partnership with Pierre Fabre continues to generate value, as we received our first milestone payment related to tab-cel regulatory progress in the U.S. in April, with the potential for additional near-term payments related to the BLA acceptance and approval."

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

Atara plans to submit a Biologics License Application (BLA) in Q2 2024 for tab-cel indicated as monotherapy for treatment of adult and pediatric patients two years of age and older with Epstein-Barr virus positive post-transplant lymphoproliferative disease (EBV+ PTLD) who have received at least one prior therapy. For solid organ transplant patients, prior therapy includes chemotherapy unless chemotherapy is inappropriate
The data package for the filing includes pivotal and supportive data covering more than 430 patients treated with tab-cel across multiple life-threatening diseases
The BLA will include the latest pivotal ALLELE study data-cut that demonstrated a statistically significant 48.8% Objective Response Rate (ORR) (p<0.0001) and favorable safety profile consistent with previous analyses
Ebvallo received regulatory approval from Swissmedic, the regulatory authority in Switzerland, further expanding its potential in Europe
Atara continues to advance the Pierre Fabre Laboratories expanded global partnership, which included approximately $27 million in cash upfront at the closing of the deal and 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
ATA3219: CD19 Program in Lupus Nephritis (LN)

Atara expects to initiate a Phase 1 study of ATA3219 as a monotherapy for the treatment of systemic lupus erythematosus (SLE) with kidney involvement (lupus nephritis [LN]) in Q4 2024 with initial clinical data anticipated in H1 2025
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 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
Atara is positioned to potentially expand ATA3219 Phase 1 study into additional autoimmune indications via the same Investigational New Drug (IND) application previously cleared for the LN study
Preclinical data supporting the potential of ATA3219 in SLE will be presented in poster presentation at the International Society for Cell & Gene Therapy meeting, which is being held May 29-June 1, 2024. The data demonstrate that ATA3219 CAR T cells led to complete CD19-specific B-cell depletion against SLE or multiple sclerosis patient peripheral blood mononuclear cells
Additional preclinical data also presented in the poster show that ATA3219 CAR T cells, which use the next-generation 1XX costimulatory domain, release lower levels of pro-inflammatory cytokines while maintaining cytotoxic function as potent as observed with autologous CAR T controls in response to stimulation with CD19+ target cells. Mitigating inflammatory cytokine release that is typically seen with standard CD19 CAR T signaling may lead to reduced toxicity and better tolerability if confirmed in clinical trials
ATA3219: CD19 Program in Severe Systemic Lupus Erythematosus (SLE) Without Lymphodepletion

Atara plans to expand the Phase 1 LN study of ATA3219 and add a new cohort in severe SLE without lymphodepletion (LD) in Q4 2024 with initial clinical data anticipated in H2 2025
The elimination of LD is designed to further simplify the treatment regimen and to potentially provide a differentiated safety profile to patients without comprising efficacy which may improve patient access
There is compelling clinical and scientific rationale supporting the potential to eliminate the need for LD based on the EBV T-cell backbone and unique features of ATA3219, including: 1) low alloreactivity risk and favorable safety in over 600 patients treated without LD, due to T-cell receptor EBV specificity and partial human leukocyte antigen matching; 2) expansion and persistence data without LD correlating to efficacy in patients treated with tab-cel; and 3) the inclusion of clinically validated features into ATA3219 such as the 1XX costimulatory domain and memory phenotype that increase potency and persistence
ATA3219: CD19 Program in Non-Hodgkin’s Lymphoma (NHL)

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
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
Previously presented preclinical data 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

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
Dual CD19 and CD20 targeting designed to address CD19 escape and tumor variability and may provide additional efficacy in lymphoma
Atara is progressing toward an IND submission in H2 2025
First Quarter 2024 Financial Results

Cash, cash equivalents and short-term investments as of March 31, 2024 totaled $46.2 million, as compared to $51.7 million as of December 31, 2023
Q1 2024 accounts receivable totaled $35.8 million and include a $20 million milestone payment related to the positive tab-cel pre-BLA meeting and approximately $12 million for the reimbursement of tab-cel global development costs from Pierre Fabre. The $20 million milestone payment was received in April 2024 and the approximate $12 million payment is expected to be received in May 2024
Together, cash, cash equivalents, short-term investments, and accounts receivable as of March 31, 2024 totaled $82.1 million
Net cash used in operating activities was $29.6 million for the first quarter 2024, as compared to $38.4 million in the same period in 2023
Q1 2024 net cash used in operating activities included 2023 annual employee bonus payments and cash disbursements related to the November 2023 and January 2024 reductions in force of approximately $13 million in aggregate
Total revenues were $27.4 million for the first quarter 2024, as compared to $1.2 million for the same period in 2023. Total revenues increased by $26.2 million year over year, primarily due to revenue recognized as a result of additional obligations for the expanded partnership with Pierre Fabre and accelerated recognition of existing deferred revenue due to the planned transition of substantially all activities relating to tab-cel at the time of BLA approval and transfer to Pierre Fabre
Total costs and operating expenses include non-cash stock-based compensation, depreciation and amortization expenses of $9.8 million for the first quarter 2024, as compared to $13.0 million for the same period in 2023
Total costs and operating expenses include restructuring expense of $4.8 million for the first quarter 2024 related to the reduction in force Atara announced in January 2024, and which reduced its headcount at that time by approximately 25% to 170 employees
Research and development expenses were $45.5 million for the first quarter 2024, as compared to $62.2 million for the same period in 2023
Research and development expenses include $4.7 million of non-cash stock-based compensation expenses for the first quarter 2024, as compared to $6.8 million for the same period in 2023
General and administrative expenses were $11.1 million for the first quarter 2024, as compared to $13.9 million for the same period in 2023
General and administrative expenses include $3.7 million of non-cash stock-based compensation expenses for the first quarter 2024, as compared to $5.0 million for the same period in 2023
Atara reported net losses of $31.8 million, or $0.23 per share, for the first quarter 2024, as compared to $74.8 million, or $0.72 per share, for the same period in 2023
Outlook and Cash Runway

Atara expects full year 2024 operating expenses to decrease by approximately 35% from 2023
The large majority of the year-over-year operating expense reduction is expected to begin in Q2 2024 and continue for the remainder of the year
Atara expects that cash, cash equivalents, short-term investments, and accounts receivable as of March 31, 2024, plus the items noted below, in total will enable funding of planned operations into 2027:
anticipated payments of $20 million and $60 million from Pierre Fabre contingent upon the successful acceptance and approval of the tab-cel BLA, respectively;
anticipated purchases of tab-cel inventory through the manufacturing transfer date by Pierre Fabre;
anticipated reimbursement for tab-cel global development costs through the BLA transfer by Pierre Fabre;
operating efficiencies resulting from completed workforce reductions;
the planned transition of substantially all activities relating to tab-cel at the time of the BLA transfer to Pierre Fabre potentially as early as Q1 2025, which will further reduce quarterly operating expenses; and
anticipated royalties from sales of tab-cel by Pierre Fabre in the U.S. post BLA approval
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.

On May 9, 2024 IN8bio, Inc. (Nasdaq: INAB), a clinical-stage biopharmaceutical company developing innovative gamma-delta T cell therapies, reported financial results for the first quarter ended March 31, 2024 and recent corporate highlights (Press release, In8bio, MAY 9, 2024, View Source [SID1234642993]).

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"We continued to make significant progress advancing our gamma-delta T cell programs in the first quarter of 2024," said William Ho, CEO and co-founder of IN8bio. "We presented new preclinical data on our nsCAR platform at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2024 Annual Meeting demonstrating its potential to target and kill various acute myeloid leukemia (AML) cells by targeting CD33 and/or CD123, while preserving healthy bone marrow cells. These findings reinforce our technology’s ability to precisely target "undruggable" cancer targets that have historically been challenging due to on-target, off-tumor toxicity. We will provide an update from our Phase 1 study of INB-100 at the 2024 European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting in June, including patient status and survival rate data. We anticipate enrolling ten additional patients in an expansion cohort at the recommended Phase 2 dose, and could potentially submit an investigational new drug (IND) application for a Phase 2 randomized control trial this year. In addition, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, we will provide an update on our Phase 1 INB-200 study in GBM which generated an initial efficacy signal supporting the INB-400 trial."

Corporate Highlights and Recent Developments

Presented data at AACR (Free AACR Whitepaper) 2024, supporting the potential of proprietary constructs targeting CD33 and/or CD123 for in vitro evaluation against various types of leukemia, including AML and chronic myeloid leukemia (CML).
Demonstrated significant differences between cells expressing traditional signaling chimeric antigen receptors (CARs) and those expressing nsCAR constructs, which include a reduction in activation-induced cell death with nsCAR constructs.
Peer-reviewed publication of "Adoptive Cell Therapy for High Grade Gliomas using Simultaneous Temozolomide and Intracranial MGMT-Modified γδ T cells Following Standard Post-Resection Chemotherapy and Radiotherapy: Current Strategy and Future Directions" in Frontiers in Immunology detailing IN8bio’s DeltEx Drug Resistant Immunotherapy (DRI) as a rational therapeutic approach for newly diagnosed GBM.
Announced first patient dosed in the Phase 2 autologous arm of INB-400 in patients with newly diagnosed GBM.
Upcoming Anticipated Pipeline Milestones and Events

American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 2024 Annual Meeting (May 10, 2024): Upcoming oral presentation: "Healthy Donor vs Patient Manufactured Autologous DeltEx DRI Product; Immunophenotyping Gene Expression," will unveil new data highlighting the characterization of our clinical manufactured DeltEx DRI product. The presentation will explore the impact of manufacturing on the final cell product from healthy donors and those manufactured from cancer patients, showcasing IN8bio’s robust capabilities and know-how in complex cell therapy process development and manufacturing.
INB-100: Report updated interim results from the ongoing Phase 1 investigator-sponsored trial at the 2024 EHA (Free EHA Whitepaper) Annual Meeting, held June 13-16 in Madrid, Spain. In addition, we will potentially submit an IND application for a Phase 2 registrational trial in 2024 in the AML and myelodysplastic syndrome (MDS) patient setting.
INB-200: Report interim Phase 1 long-term follow up results in GBM at multiple medical meetings in 2024 including at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting.
INB-400: Initiated patient dosing in the Phase 2 autologous arm of INB-400 in newly diagnosed GBM. IN8bio expects to treat up to a total of 40 patients in arm A at multiple sites across the United States.
First Quarter 2024 Financial Highlights

Research and Development (R&D) expenses: R&D expenses were $4.9 million, compared to $4.4 million for the comparable prior year period. The increase was primarily due to (i) increased personnel-related costs, including salaries and stock-based compensation due to increased headcount and (ii) direct clinical costs for INB-100, INB-200 and INB-400.
General and administrative expenses: General and administrative expenses were $3.7 million, compared to $3.5 million for the comparable prior year period. The increase was primarily due to increased personnel-related costs, including stock-based compensation and rent, offset by cost savings related to directors’ and officers’ insurance premiums and a reduction in professional services.
Net loss: Net loss was $8.6 million, or $0.20 per basic and diluted common share, compared to a net loss of $7.5 million, or $0.30 per basic and diluted common share, for the comparable prior year period.
Cash position: As of March 31, 2024, the Company had cash of $13.0 million, compared to $21.3 million, as of December 31, 2023.