On January 18, 2022 Humanigen, Inc. (Nasdaq: HGEN) ("Humanigen"), a clinical-stage biopharmaceutical company focused on preventing and treating an immune hyper-response called ‘cytokine storm,’ reported a peer-reviewed publication in the Journal of Medical Economics (View Source) citing the clinical and associated health economic benefits of lenzilumab (Press release, Humanigen, JAN 18, 2022, View Source [SID1234605654]). The publication demonstrated, in all cases, lenzilumab plus SOC improved all specified clinical outcomes compared with SOC alone. Lenzilumab plus SOC, resulted in an estimated cost savings of $13,190 per patient (net savings of $3,190, after an assumed price of $10,000 for lenzilumab) in those receiving remdesivir with baseline C-Reactive Protein (CRP) levels <150 mg/L, and aged <85 years, the primary analysis population in the fully enrolled ACTIV-5/BET-B study. In other subpopulations, per-patient savings were also observed, including those aged <85 years with baseline CRP <150mg/L with or without remdesivir (cost savings = $11,858, net cost savings = $1,858) and within the subpopulation of Black/African American patients with baseline CRP <150mg/L (cost savings = $23,154, net cost savings = $13,154).

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"This publication demonstrates the opportunity to realise significant cost savings for healthcare systems, while also improving outcomes for patients," said Dr. Adrian Kilcoyne, Chief Medical Officer, Humanigen. "With the current omicron surge, the importance of variant-agnostic and both clinically effective and cost-effective therapies is paramount."

This peer-reviewed publication highlights the significant costs of treating hospitalized COVID-19 patients and the economic benefits of potentially improving survival without ventilation, ventilator use, time to recovery, mortality, time in the ICU, and time to invasive mechanical ventilation, which may be associated with adding lenzilumab to standard of care from the US hospital perspective.

"During these unprecedented and challenging times, we are preparing to commercialize lenzilumab as a single day treatment which is variant-agnostic and, if authorized, a driver of clinical and economic value to patients and healthcare systems," said Edward P. Jordan, Chief Commercial Officer, Humanigen.

On January 18, 2022 A2 Biotherapeutics reported the Tmod system exploits irreversible genetic changes in cancer cells called loss of heterozygosity (LOH) (Press release, A2 Biotherapeutics, JAN 18, 2022, View Source [SID1234605600]). A2 Bio will be presenting on Saturday, January 22nd at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal (GI) Cancers Symposium taking place virtually and in-person on January 20–22, 2022, at the Moscone Center in San Francisco, CA.

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A2 Bio in partnership with Tempus, a leader in artificial intelligence and precision medicine, analyzed the Tempus xT NGS assay database that has over 21,000 samples with HLA locus LOH data and over 10,000 of which are from patients with advanced disease stage ≥ 3; 3,000 of these samples are from GI cancer patients. These results demonstrate clonal frequency of HLA LOH in advanced GI solid tumor cancers of 16.3%, with a range of 15.6%-20.8% among colorectal, pancreatic, and gastroesophageal tumors. In addition, these frequencies are similar to primary tumors from The Cancer Genome Atlas (TCGA) database. Thus, HLA LOH is a well-defined discriminator between tumor and normal cells and can be exploited for NOT logic-gated Tmod CAR T to reduce on-target off-tumor toxicity. These results expand knowledge about HLA LOH in these tumors and pave the way for the use of Tempus xT NGS in screening patients for future Tmod CAR T cell therapy.

"A2 Bio has developed Tmod CAR T, which targets clonal HLA LOH as a clear differentiator between normal versus tumor cells," said William Go, MD, PhD, Chief Medical Officer at A2 Bio. "The Tempus xT next generation sequencing assay will be utilized in BASECAMP-1. BASECAMP-1 is a study to identify HLA LOH solid tumor cancer patients and obtain their T cells earlier in their treatment paradigm who may benefit from future carcinoembryonic antigen (CEA) and mesothelin (MSLN) Tmod CAR T therapy. Novel therapies are sorely needed in GI malignancies, especially in pancreatic cancer, where limited therapeutic advances have been made in over two decades."

Lead author J. Randolph Hecht, MD, Professor of Clinical Medicine, Director of the UCLA Gastrointestinal Oncology Program and principal investigator of the BASECAMP-1 trial, stated: "Tmod CAR T is an elegant and truly novel therapeutic utilizing a NOT logic gate to distinguish between normal and tumor cells. While other T cell therapies have failed in GI cancers due to toxicity or lack of efficacy, targeting HLA LOH with Tmod may provide the therapeutic safety window necessary for clinically significant outcomes. In addition, patients who might benefit from this approach can be identified using the widely used Tempus xT NGS assay early in the course of their disease."

ASCO GI Poster Information

Title: Next generation sequencing (NGS) to identify relapsed gastrointestinal (GI) solid tumor patients with human leukocyte antigen (HLA) loss of heterozygosity (LOH) for future logic-gated CAR T therapy to reduce on target off tumor toxicity

Presenter: J. Randolph Hecht, MD, Director of the UCLA Gastrointestinal Oncology Program

Session: Poster Session C: Cancers of the Colon, Rectum, and Anus.

Date/Time: Saturday, January 22 at 6:30 am to 7:55 am and 12:30 pm to 2:00 pm PT

Location: Abstract 190 – Level 1, West Hall; Moscone Center, San Francisco, CA

A2 Bio’s posters presented can be viewed on the company’s website at www.a2bio.com/science/abstracts-and-publications.

On January 18, 2022 Akeso reported that Ligufalimab combined with Ivonescimab has obtained approval from the Center for Drug Evaluation (CDE) of the National Medical Products Administration of the People’s Republic of China (”China”) to initiate a Phase Ib/II clinical trial with or without chemotherapy for the treatment of advanced malignant tumors, with an aim to evaluate the safety, tolerability, pharmacokinetics, immunogenicity and anti-tumor activity of Ligufalimab combined with Ivonescimab combined with or without chemotherapy for the treatment of advanced malignant tumors (Press release, Akeso Biopharma, JAN 18, 2022, View Source [SID1234605606]).

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The main target subjects of the phase II clinical trial were patients with gastrointestinal tumors. Previously, a phase Ib/II clinical trial of Ligufalimab combined with Ivonescimab has been initiated with main target subjects of patients with head and neck malignant tumors.

Related statistics have shown that malignant tumors have become the major cause of death in the population of China, where deaths from malignant tumors account for approximatelyn23.91% of deaths from all causes of the population. The five-year relative survival rate of malignant tumors in China is approximately 40.5%, which is still far from developed countries. In addition, gastrointestinal tumors account for six out of the top ten death rate of advanced malignant tumors. Among which, treatments for advanced gastric cancer, biliary malignant tumors, pancreatic cancer and other common gastrointestinal tumors are limited and the efficacy is not high, resulting in a huge gap of clinical demand.

Related studies have shown that Ivonescimab can simultaneously stimulate anti-tumor immune response and inhibit tumor angiogenesis through activation of T cells. Since the over-expression of VEGF in the tumor microenvironment has immunosuppressive effects, the use of a bi-specific antibody that blocks both PD-1 and VEGF can achieve synergistic anti-tumor effects of PD-1/PD-L1 antibodies and anti-VEGF antibodies. It is expected to achieve good clinical efficacy and safety. Currently, anti-PD-1/PD-L1 antibody drugs on the market or under research combined with chemotherapy has shown certain clinical benefits for gastrointestinal tumors. For non-small cell lung cancer and hepatocellular carcinoma, the combination of anti-PD-1/PD-L1 antibodies with anti-VEGF antibodies has shown notable synergistic effects.

Related studies have also shown that combination therapy with anti-PD-1 drugs and targeted CD47 drugs yields synergistic antitumor effect through activation of both innate and adaptive immune response, and has demonstrated satisfactory anti-tumor effect in some of the patients with solid tumors with no additional safety risk. CD47 up-regulation can inhibit the phagocytosis of macrophages and the anti-tumor effect of VEGF/VEGFR inhibitors. At the same time, anti-VEGF/VEGFR treatment can also induce CD47 up-regulation, thereby inhibiting the anti-tumor function of macrophages. Therefore, blocking both VEGF and CD47 can effectively inhibit the immunosuppressive pathway induced by anti-angiogenesis therapy (CD47 up-regulation) while enhancing the phagocytosis of macrophages to improve the anti-tumor efficacy.

Therefore, the combination therapy of Ligufalimab and Ivonescimab is expected to activate both innate and adaptive immune pathways, so to achieve the synergistic effect of inhibiting the three tumor immune targets of PD-1, VEGF and CD47 through the combination of the two drugs, thus achieving better anti-tumor effects as compared with existing therapies. Furthermore, based on the statistics of the in vitro and in vivo pharmacodynamics and toxicology studies of Ligufalimab and Ivonescimab, the anti-tumor activity and the controlled safety profile in several clinical trials of different types of tumors, it is expected that the combination of Ivonescimab and Ligufalimab and/or chemotherapy will have a positive effect for the treatment of gastrointestinal tumors.

Currently, Ivonescimab has taken the lead in entering the phase III clinical trial globally, and Ligufalimab is also one of the world’s leading CD47 monoclonal antibodies in clinical research and development progress. The clinical trial of Ligufalimab combined with Ivonescimab in the treatment of head and neck malignant tumors and gastrointestinal tumors is another embodiment of the Company’s continuous exploration of the clinical and commercial value of its rich drug pipeline.

On January 18, 2022 I-Mab reported that the first patient has been dosed in its China Phase II trial of lemzoparlimab in combination with the PD-1 antibody toripalimab (TUOYI) in patients with advanced solid tumors (Press release, I-Mab Biopharma, JAN 18, 2022, View Source [SID1234605605]). The phase 2 study is designed as a basket trial and could potentially lead to a registrational trial in China.

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"We are pleased to initiate the phase 2 trial for the combination of lemzoparlimab and toripalimab in patients with advanced solid tumors in China, and looking forward to accelerating its clinical development," said Dr. Andrew Zhu, President at I-Mab. "We are leveraging our translational medicine findings to select tumors with a higher probability of success for this trial."

Lemzoparlimab is a novel CD47 antibody that exerts strong anti-tumor activity while exhibiting minimal binding to red blood cells based on pre-clinical data. It is being evaluated in combination with pembrolizumab (Keytruda) in advanced solid tumors in the U.S. and in patients with NHL and AML/MDS in other ongoing clinical studies in the U.S. and China. In all clinical trials conducted so far, lemzoparlimab has been administered without a priming dose.

About CD47 and Lemzoparlimab

CD47 is a cell surface protein over-expressed in a wide variety of cancers and can act to protect tumors by delivering a "don’t eat me" signal to otherwise tumor-engulfing macrophages. CD47 antibody blocks this signal and enables macrophages to attack tumor cells. However, development of CD47 antibody as a cancer therapy has been hampered by its hematologic side effects, such as severe anemia, caused by natural binding of CD47 antibody to red blood cells. Scientists at I-Mab discovered a novel CD47 antibody, lemzoparlimab, that is designed to target tumor cells while exerting a minimal untoward effect on red blood cells.

Multiple clinical studies are ongoing in both the U.S. and China to explore indications in treating both hematologic malignancies and solid tumors. Lemzoparlimab is being studied in patients with myelodysplastic syndrome (MDS), acute myelocytic leukemia (AML), and advanced solid tumors in combination with chemotherapy and immune checkpoint inhibitors in the U.S. and China. Combined clinical results from these studies could potentially support future registrational trials in China.

In September 2020, I-Mab and AbbVie entered into a global strategic collaboration to develop and commercialize lemzoparlimab. This includes the design and conduct of further clinical trials to evaluate lemzoparlimab in multiple cancers in China and globally. AbbVie has assumed sponsorship of the U.S. study as of April 2021.

On January 18, 2022 Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, reported updates and anticipated milestones across its 2022 strategic objectives (Press release, Turning Point Therapeutics, 18 18, 2022, View Source [SID1234605604]).

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"As we look to 2022, we are focused on continuing progress across our clinical stage pipeline and expanding our discovery engine," said Athena Countouriotis, M.D., president and CEO. "We are encouraged that all six cohorts in our registration enabling TRIDENT-1 study for our lead drug candidate repotrectinib continue to enroll at a strong pace and we look forward to providing topline BICR data from the ROS1-positive NSCLC cohorts in the second quarter of this year. With our strong balance sheet and organizational growth and leadership, we are well positioned to continue to make rapid progress across our entire portfolio."

The company’s key strategic priorities are:

1. ADVANCE REPOTRECTINIB PROGRAM

The company announced today that the Phase 2 registration enabling TRIDENT-1 study had strong progress across all cohorts for enrollment during the fourth quarter of 2021 with expansion cohort 4 (EXP-4 — ROS1-positive advanced NSCLC population pretreated with one prior TKI without chemotherapy) now fully enrolled with the targeted 60 patients. Enrollment across all six cohorts of the study remains open and continues to progress steadily. Enrollment in EXP-4 is ongoing to provide continued access to new patients.

Data from ROS1-positive TKI-naïve NSCLC patients in the Phase 1 portion of the TRIDENT-1 trial continue to demonstrate best-in-class potential. The duration of response (DOR) for 6 responder patients, among a total of 7 patients treated at or above the recommended Phase 2 dose, ranged from 5.6 to 42.2+ months with 3 patients who had DOR of greater than 30 months. DOR was calculated using blinded independent central review (BICR) assessments as of the data cut-off date of July 22, 2019 followed by physician assessments as of the data cut-off date of November 29, 2021. Duration of treatment for the 7 patients ranged from 10.9 to 45.8+ months with 4 out of 7 patients remaining on treatment for greater than 3 years as of the data cut-off date of November 29, 2021.

The company anticipates discussing with the U.S. Food and Drug Administration (FDA) topline BICR data from all of the ROS1-positive NSCLC cohorts from TRIDENT-1 at a pre-NDA meeting in the second quarter of 2022.The company plans on reporting the BICR results, including both objective response rate (ORR) and DOR, in the second quarter of 2022 prior to the pre-NDA meeting.

The company anticipates providing a clinical data update from the NTRK-positive advanced solid tumor cohorts from TRIDENT-1 in the second half of 2022.

2. ADVANCE OTHER PIPELINE PROGRAMS

ELZOVANTINIB (TPX-0022), MET/SRC/CSF1R INHIBITOR

Patient enrollment continues in the SHIELD-1 study at 40 mg QD to 40 mg BID in Phase 1 dose expansion and in parallel elzovantinib also is being studied at an intermediate dose level (60 mg QD to 60 mg BID) in Phase 1 dose escalation.
The company anticipates providing a clinical data update from the Phase 1 SHIELD-1 study in the second half of 2022.
The company anticipates initiating the Phase 2 portion of the SHIELD-1 study in the second half of 2022, pending FDA feedback on data from the intermediate dose level.

The company anticipates initiating the SHIELD-2 combination study of elzovantinib and aumolertinib in mid-2022, pending clearance of an investigational new drug (IND) application by the FDA.

Aumolertinib is EQRx, Inc.’s drug candidate targeting EGFR, and the combination of aumolertinib and elzovantinib will be studied in this Phase 1b/2 trial in patients with EGFR mutant MET-amplified advanced NSCLC who have progressed following treatment with osimertinib. The study will evaluate the safety, tolerability and preliminary efficacy of the combination regimen.
TPX-0046, RET INHIBITOR

The company continues to progress the dose-finding portion of the Phase 1/2 SWORD-1 study, where the company is evaluating multiple doses and schedules to further characterize the pharmacokinetics, safety, and efficacy profile before determining the RP2D.
TPX-0131, ALK INHIBITOR

The dose finding portion of the Phase 1/2 FORGE-1 study is ongoing. The company anticipates providing early interim data from initial patients treated in the dose-finding portion of the FORGE-1 study in the fourth quarter of 2022 or early 2023.
3. ADVANCE RESEARCH PROGRAMS

The company remains on track to nominate two development candidates in the second half of 2022. The company currently has four internal discovery programs targeting aberrant GTPase signaling known to drive genomically defined cancers with significant unmet medical need. The most advanced programs target KRAS G12D and the p21 activated kinase, or "PAK" family.

The company also plans on providing details on the other 2 GTPase signaling discovery programs during the second half of 2022.
FINANCIAL UPDATE

Based on its current operating plans, the company expects that its cash, cash equivalents and marketable securities of $975-985 million as of December 31, 2021 (unaudited), are sufficient to fund current operations into the second half of 2024.