On May 5, 2022 Avalo Therapeutics, Inc. (Nasdaq: AVTX), reported business updates and first quarter 2022 financial results (Press release, Avalo Therapeutics, MAY 5, 2022, View Source [SID1234613679]).

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"The first quarter has been highly productive for the Avalo Therapeutics team. We executed our pipeline prioritization plan and right-sized the organization needed to deliver what we think will provide the greatest value for our shareholders," said Dr. Garry Neil, Chief Executive Officer of Avalo Therapeutics. "We remain focused on driving our highest value programs forward to meet our timelines. These include our Phase 2 clinical trial of AVTX-002 in NEA and our pivotal trial of ATX-803 in LAD II. We have now initiated both programs, and we expect to dose our first patients in both studies in the second quarter, keeping the programs on track to meet our year-end data release milestones."

Business Update

The Company executed a reduction in workforce in March to align with its previously announced, focused pipeline. With these changes, the Company believes it will achieve substantial cost savings over time while creating a more appropriately sized workforce needed to successfully achieve the Company’s 2022 objectives, most notably obtaining and releasing data for its Phase 2 clinical trial of AVTX-002 in NEA and pivotal trial of AVTX-803 in LAD II. Headcount was reduced by approximately one third from December 31, 2021.
Program Updates and Milestones:

AVTX-002: Anti-LIGHT monoclonal antibody (mAb) targeting immune-inflammatory diseases.
NEA: The Company has initiated its Phase 2 randomized, double-blind, placebo-controlled clinical trial evaluating AVTX-002 in 80 patients with poorly controlled NEA. Top-line data from the trial are expected in the fourth quarter of 2022.
IBD: The Company continues to consider initiating a randomized, double-blind, placebo-controlled clinical study in moderate-to-severe refractory patients in inflammatory bowel disease (IBD).

AVTX-007: Anti-IL-18 mAb targeting adult-onset Still’s disease (AOSD).

AOSD: The Company is evaluating AVTX-007 in a multicenter, Phase 1b study in 12 refractory or steroid-dependent patients with AOSD in two cohorts. Management is currently reviewing preliminary data and the path forward related to this indication. Top-line data are currently expected in 2023, which is subject to change and refinement pending finalization of the review.
AVTX-800 programs (AVTX-801 and AVTX-803): Monosaccharide therapies for two congenital disorders of glycosylation (CDGs): leukocyte adhesion deficiency type II (LAD II, also known as SLC35C1-CDG) and PGM1-CDG.
LAD II: The Company has initiated a single-center (U.S.), double-blind (followed by an open-label extension) pivotal study of AVTX-803 in patients with LAD II. Data from this pivotal trial are expected in the fourth quarter of 2022.
PGM1-CDG: Avalo and the study sponsor remain in dialogue with the U.S. Food and Drug Administration (FDA) to align on a suitable clinical study design for AVTX-801 (PGM1-CDG). Pivotal trial data are expected in 2023. Avalo is currently working with the study sponsor to refine milestone timing.
First Quarter 2022 Financial Update:

As of March 31, 2022, Avalo had $38.5 million in cash and cash equivalents, representing a $16.1 million decrease as compared to December 31, 2021. The decrease was primarily driven by operating expenditures to fund and support pipeline development.

Total operating expenses decreased $9.0 million for the three months ended March 31, 2022 as compared to the three months ended March 31, 2021. The decrease was mainly driven by a $15.6 million decrease in research and development expenses. The decrease in research and development expenses was due to: 1) a $10.0 million upfront license fee incurred in the first quarter of 2021, which did not repeat; and 2) a $5.6 million reduction due to specific timing of manufacturing and clinical trial activities.

The decrease in operating expenses was partially offset by $3.1 million of severance expense and $4.3 million of non-cash stock-based compensation expense recognized in the first quarter of 2022 due to headcount reductions from the pipeline prioritization plan and the termination of employees prior to such plan. Most of these expenses were general and administrative, and they were the primary driver of the increase in general and administrative expenses period over period. The Company expects salary related expenses to decrease beginning in the second quarter as a result of the headcount reductions. The net loss and change in net loss was largely driven by operating expenses.

(a) The condensed consolidated balance sheets as of March 31, 2022 and December 31, 2021 have been derived from the reviewed and audited financial statements, respectively, but do not include all of the information and footnotes required by accounting principles accepted in the United States for complete financial statements.

(a) The unaudited condensed consolidated statements of operations for the three months ended March 31, 2022 and 2021 have been derived from the reviewed financial statements but do not include all of the information and footnotes required by accounting principles generally accepted in the United States for complete financial statements.

On May 5, 2022 Biogen Inc. (Nasdaq: BIIB) and MedRhythms reported that they have entered into a license agreement to develop and commercialize MR-004, an investigational prescription digital therapeutic for the potential treatment of gait deficits in multiple sclerosis (MS) (Press release, Biogen, MAY 5, 2022, View Source [SID1234613695]). The collaboration combines MedRhythms’ digital expertise with Biogen’s leadership and global footprint in MS in order to address significant unmet patient needs.

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MedRhythms is developing next-generation prescription digital therapeutics across a broad range of indications in neurology via a technology platform that leverages advancements in neuroscience and music to target improved walking and mobility. MR-004 is MedRhythms’ pipeline candidate in MS, which aims to improve gait and gait-related aspects of movement, potentially providing MS patients with improved independence related to mobility. If approved, MR-004 has the potential to become the first prescription digital therapeutic for gait deficit in MS. MedRhythms is currently conducting two ongoing feasibility studies for MR-004, and, based on the readout of the first study, plans to initiate a registrational trial in the near future.

"As part of our aspiration in digital health, together with MedRhythms we aim to advance a new, innovative treatment option for people living with MS that may help address walking impairment, a common issue that impacts their overall quality of life," said Martin Dubuc, Head of Biogen Digital Health. "Pioneering in digital therapeutics exemplifies Biogen’s commitment to advance novel therapies that we hope will improve outcomes for people living with MS."

"At MedRhythms, we are committed to redefining what is possible for people living with neurologic diseases by building evidence-based products that meaningfully impact symptoms that have been underserved by traditional treatment modalities," said Brian Harris, Chief Executive Officer of MedRhythms. "We look forward to what our collaboration with Biogen, a global leader in MS, could mean for the patients we serve around the world."

Under the terms of the agreement, Biogen will make an upfront payment of $3 million to MedRhythms. Should certain development and commercial milestones be achieved, MedRhythms will be eligible to receive up to $117.5 million in potential milestone payments. MedRhythms is also eligible to receive tiered royalties in the high-single digits to low-teens on potential global sales.

On May 15, 2022 Elpiscience Biopharmaceuticals, Inc. ("Elpiscience"), a clinical-stage biopharmaceutical company focused on developing next-generation immunotherapies to benefit cancer patients worldwide, reported partner Compass Therapeutics reported positive interim ES104 (also known as CTX-009) Phase 2 data in combination with paclitaxel in patients with biliary tract cancers (BTC) (Press release, Elpiscience, MAY 5, 2022, View Source [SID1234613705]). ES104 is a bispecific antibody that simultaneously blocks Delta-like ligand 4/Notch (DLL4) and vascular endothelial growth factor A (VEGF-A) signaling pathways, which are critical to angiogenesis and tumor vascularization.

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In the study, ES104 demonstrated:

42% overall response rate (ORR) based on 10 patients with Partial Responses (PRs), including 9 PRs confirmed by RECIST 1.1 and 1 PR pending confirmation
Anti-tumor activity in previously treated patients with a clinical benefit rate (CBR) of 92% based on 22 patients with a PR or stable disease (SD) out of 24 enrolled patients
Well-tolerated and preliminary safety profile consistent with prior studies
The Phase 2 study in patients with BTC is currently being conducted at four leading medical centers in Korea and Compass Therapeutics plans to open additional sites in the United States. In China, Elpiscience is currently enrolling patients in a ES104 Phase 1/2 study for the treatment of unresectable locally advanced or metastatic colorectal cancer (CRC). ES104 is currently the only clinical-stage bispecific antibody targeting VEGF and DLL4 in China.

"We are encouraged by the impressive interim Phase 2 data in BTC patients from our partner," said Steve Chin, Chief Medical Officer of Elpiscience. "ES104 in combination with paclitaxel showed a high ORR including responses in all four BTC subtypes and good overall tolerability consistent with prior studies. We believe in the clinical strategy to simultaneously target VEGF and DLL4 and look forward to our study findings in advanced CRC patients."

For more information on the Phase 1/2 clinical study in patients with unresectable locally advanced or metastatic CRC, refer to Clinicaltrials.gov identifier NCT05167448.

About ES104

ES104 is a bispecific antibody that simultaneously blocks Delta-like ligand 4/Notch (DLL4) and vascular endothelial growth factor A (VEGF-A) signaling pathways, which are critical to angiogenesis and tumor vascularization. Pre-clinical and early clinical data of ES104 show that blocking both pathways provides robust anti-tumor activity across several solid tumors, including colorectal, gastric, cholangiocarcinoma, pancreatic, and non-small cell lung cancer. Partial responses to ES104 as monotherapy have been observed in heavily pre-treated cancer patients, who were resistant to currently approved anti-VEGF therapies. ES104 has completed a Phase 1 monotherapy dose-escalation and expansion study (NCT03292783). Phase 1b and Phase 2 clinical studies (NCT04492033) in combination with chemotherapy are ongoing. Elpiscience licensed ES104 greater China rights from Compass Therapeutics in January 2021 and is conducting Phase 1/2 study in China for treatment in patients with unresectable locally advanced or metastatic colorectal cancer.

On May 5, 2022 Arcellx, Inc. (NASDAQ: ACLX), a biotechnology company reimagining cell therapy through the development of innovative immunotherapies for patients with cancer and other incurable diseases, reported that management will participate in a fireside chat at the BofA Securities 2022 Healthcare Conference on Wednesday, May 11, 2022, at 5:00 p.m. E.T (Press release, Arcellx, MAY 5, 2022, View Source [SID1234613727]).

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A live webcast of the discussion will be accessible from Arcellx’s website at www.arcellx.com in the Investor section. A replay of the webcast will be archived and available for 30 days following the event.

On May 5, 2022 Gritstone bio, Inc. (Nasdaq: GRTS), a clinical-stage biotechnology company that aims to develop the world’s most potent vaccines, reported financial results for the first quarter ended March 31, 2022 and reviewed business highlights (Press release, Gritstone Oncology, MAY 5, 2022, View Source [SID1234613753]).

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"Clinical data out of our cancer and viral disease vaccine programs are expected to be flowing steadily through year-end and over the next 18 months," said Andrew Allen, M.D., Ph.D., Co-founder, President and Chief Executive Officer of Gritstone. "Our individualized neoantigen vaccine candidate for solid tumors, GRANITE, is now in a randomized Phase 2/3 trial in newly diagnosed metastatic colorectal cancer, building on the exciting molecular response/survival data shown at ESMO (Free ESMO Whitepaper) 2021 in end-stage colorectal cancer patients. Multiple Phase 1 trials are ongoing in CORAL (2nd generation COVID-19 vaccine program) with data from all studies expected throughout 2H2022, and initial data from the Phase 2 study of SLATE-KRAS (KRAS-specific ‘off-the-shelf’ vaccine candidate) is also expected in 2H2022. Our recent presentations at AACR (Free AACR Whitepaper) underscore the unique capabilities of our novel self-amplifying mRNA (samRNA) vector, which has demonstrated potency and dose sparing potential along with a favorable safety and tolerability profile in the clinic. The data we are generating with SARS-CoV-2 as the target are providing validation for the entire samRNA platform and provide clear rationale to pursue additional viral pathogens. We look forward to sharing more data and continuing to demonstrate the value we are bringing to patients and all stakeholders as the year progresses."

Clinical Program Updates

Tumor-Specific Neoantigen (TSNA) Oncology Programs

GRANITE – Individualized, TSNA-directed vaccine-based immunotherapy using an adenoviral priming vector and samRNA boost vector to deliver relevant neoantigens. Following success in late-line studies, Gritstone intends to continue advancing GRANITE through randomized, controlled trials and evaluate these candidates in earlier lines of treatment, where immune responses may be stronger and the potential benefits could be further accentuated.

In January, Gritstone announced the first patient was enrolled for inclusion in GRANITE-CRC-1L, a randomized, controlled Phase 2/3 trial evaluating GRANITE in combination with immune checkpoint blockade for frontline maintenance treatment of newly diagnosed patients with metastatic, microsatellite-stable colorectal cancer (MSS-CRC). Preliminary data (molecular response and progression-free survival) from the Phase 2 portion of the trial are expected in 2H2023.
In March, Gritstone announced the first patient was enrolled for inclusion in GRANITE-CRC-ADJUVANT, a randomized, controlled Phase 2 trial in patients with high risk MSS-CRC and stage II/III disease who are circulating tumor DNA (ctDNA)+ after definitive surgery.
In April, Gritstone shared two poster presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting:
Poster 1238 further demonstrated the correlation between patient survival and ctDNA in metastatic CRC.
Poster 4149 demonstrated lower doses of samRNA drive superior neoantigen-specific CD8+ T cell responses in cancer patients versus high doses in Phase 1/2 trials for GRANITE and SLATE in patients with advanced solid tumors.
SLATE – "Off-the-shelf" shared neoantigen-directed vaccine-based immunotherapy using an adenoviral priming vector and samRNA boost vector to deliver a cassette of shared TSNA. Gritstone intends to continue advancing its existing candidate, SLATE-KRAS, and has a long-term objective of developing a suite of "off-the-shelf" product candidates that target tumor-specific targets across a number of patient populations and cancer types.

In April, Gritstone presented an oral presentation at AACR (Free AACR Whitepaper) detailing how translational immunology data and the company’s cassette design capabilities enabled development of SLATE-KRAS, an optimized, KRAS-specific version of SLATE that is now in Phase 2 study in patients with advanced non-small cell lung cancer (NSCLC) and CRC.
Early signals from the ongoing Phase 2 study support the potential of SLATE-KRAS to drive stronger CD8+ T cell responses to mutant KRAS than our original candidate, SLATE v1.
Initial data from the ongoing Phase 2 study of SLATE-KRAS trial are expected in 2H2022.
Infectious Disease Programs

Gritstone’s infectious disease programs aim to deliver vaccine candidates that drive both B cell and T cell immunity with the potential to provide either a protective or therapeutic effect across a broad array of viral diseases. This approach has demonstrated the ability to generate robust CD8+ T cells and neutralizing antibodies against SARS-CoV-2 in multiple preclinical and clinical studies and is being evaluated against multiple other pathogens in Gritstone-owned and partnered studies.

CORAL – Second-generation SARS-CoV-2 vaccine program delivering both spike and highly conserved non-spike T cell epitopes (TCEs) with a focus on the samRNA vector. This approach offers potential for more durable clinical protection and broader immunity against SARS-CoV-2 variants than first generation products by inducing potent CD8+ T cells in addition to neutralizing antibody responses.

Gritstone is currently evaluating five distinct SARS-CoV-2 product candidates across four different clinical trials containing Spike plus additional non-Spike TCE sequences (and also full-length nucleocapsid). These studies include homologous and heterologous prime-boost regimens. All four of these studies are ongoing, and initial data from all are expected during the second half of 2022.
The CORAL-BOOST study, a Phase 1 study evaluating a T cell enhanced samRNA vaccine as a booster against SARS-CoV-2, is ongoing in the United Kingdom. In January, Gritstone announced positive clinical data from the first cohort and subsequently expanded the study. The data, which demonstrated both strong neutralizing antibody responses to Spike and robust CD8+ T cell responses, provided human proof of concept of the samRNA vector in viral diseases and the company’s approach to infectious disease.
The CORAL-CEPI trial is ongoing in South Africa with support from the Coalition for Epidemic Preparedness Innovations (CEPI) and is evaluating T cell enhanced omicron- and beta-spike constructs in virus-naïve, convalescent, and HIV+ patients.
The CORAL-IMMUNOCOMPROMISED trial is ongoing in the United Kingdom evaluating T cell enhanced samRNA and chimpanzee adenovirus (ChAd) vaccines in B cell deficient subjects.
The CORAL-NIH trial, which is being sponsored and executed by the National Institute of Allergy and Infectious Disease (NIAID), is ongoing in the United States evaluating T cell enhanced samRNA and/or ChAd vaccines in previously vaccinated healthy volunteers.
HIV – Collaboration with Gilead Sciences, Inc (Gilead) under Gilead’s HIV Cure Program to research and develop vaccine-based HIV immunotherapy treatment

An investigational new drug application (IND) was cleared in December 2021.
First Quarter 2022 Financial Results

Cash, cash equivalents, marketable securities and restricted cash were $186.8 million as of March 31, 2022, compared to $223.5 million as of December 31, 2021.

Research and development expenses were $28.2 million for the three months ended March 31, 2022, compared to $24.9 million for the three months ended March 31, 2021. The increase of $3.3 million for the three months ended March 31, 2022 compared to the three months ended March 31, 2021 was primarily due to increases in personnel-related expenses, outside services, and facilities related costs, offset by decreases in laboratory supplies and milestone and license payments.

General and administrative expenses were $8.0 million for the three months ended March 31, 2022, compared to $6.9 million for the three months ended March 31, 2021. The increase of $1.1 million was primarily attributable to increases in personnel-related expenses and in facilities-related costs, offset by a decrease in outside services.

Collaboration and license revenue was $4.7 million for the three months ended March 31, 2022, compared to $39.7 million for the three months ended March 31, 2021. During the three months ended March 31, 2022, we recognized $4.0 million in collaboration revenue related to the 2seventy Agreement, $0.7 million in collaboration revenue related to the Gilead Collaboration Agreement, $2.2 million in grant revenue from the CEPI Funding Agreement, and $0.2 million in grant revenue from the Gates Foundation. During the three months ended March 31, 2021, we recorded $38.6 million in license revenue and $0.3 million in collaboration revenue related to the Gilead Collaboration Agreement and $0.7 million in collaboration revenue related to the 2seventy Agreement.