On March 28, 2022 Avera Health (Avera), an integrated regional health care system that serves 300 locations across the Upper Midwest, and Theralink Technologies (OTC: THER) ("Theralink" or the "Company"), a precision medicine company with a novel phosphoprotein-based assay for breast cancer reported a strategic collaboration to advance comprehensive molecular profiling, enabling Avera Health’s providers and patients to benefit from data-driven insights that inform targeted cancer treatments (Press release, Avera Pharmaceuticals, MAR 28, 2022, View Source [SID1234611072]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Avera has a long-standing history of leading the way in precision oncology with patients’ tumors being genetically sequenced to guide individualized cancer care. Theralink, with its patented protein and phosphoprotein biomarker platform and lab developed test, is the only commercially available assay for clinical use that measures the tumor cell levels of activated proteins, which are the primary targets of most FDA-approved therapies and biopharmaceutical investigational drugs.

Theralink will provide key patient-specific information about which drug targets are activated and "in use" in each patient tumor sample. This information, coupled with the genomics findings, will provide a comprehensive molecular profile for all Avera oncology patients by way of a multiomic report used for physician treatment decisions.

"Avera has been a cancer care leader in our region for many years. Avera Cancer Institute is focused on actionable insights for our physicians and patients to make treatment decisions that are personalized," said Casey Williams, Chief Scientific Officer and Executive Director of Cancer Research. "We understand the role this innovative approach plays in generating better health outcomes for our patients, and Theralink will play a key role in that process."

"We believe that the Theralink protein/phosphoprotein data, combined with the next generation sequencing data, may give Avera Cancer Institute the most cutting edge and best precision oncology data in the world, potentially creating a step change in cancer care," said Mick Ruxin, M.D., President & CEO of Theralink. He went on to say, "It is gratifying to know that a large, prestigious, midwest cancer program, Avera Health, has realized the significant potential value of our Theralink assay for their cancer patients." Dr. Ruxin continued, "We expect great results from working with Avera and their patients in our goal to decrease the morbidity and mortality of cancer patients."

As part of this collaboration, Avera will assist Theralink Technologies in validating new clinical assays for additional tumors (such as GYN, Head and Neck, GI, Lung, Kidney, Liver and Prostate) through retrospective case analysis and population-based data. This may bring new capability and insights to precision oncology care and allow for the Theralink assay to become a pan-tumor assay.

On March 28, 2022 GT Biopharma, Inc. (the "Company") (NASDAQ: GTBP), a clinical stage immuno-oncology company focused on developing innovative therapeutics based on the Company’s proprietary natural killer (NK) cell engager, TriKE platform, reported fourth quarter and full-year 2021 results for the period ended December 31, 2021 (Press release, GT Biopharma, MAR 28, 2022, View Source [SID1234611071]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We’re excited for GTB-3650’s prospects in the new year as we advance the Company’s second-generation Tri-specific NK cell engager (TriKE) technology into an IND-enabling study. The development of GTB-3650, our lead-asset second generation nanobody TriKE has been significantly de-risked, propelled by GTB-3550 predecessor data published in 2021 including: positive first-in-human Phase 1 data; and in-vivo animal model data, conducted in combination with a bispecific killer cell engager asset," said Michael Breen, Executive Chairman and Interim Chief Executive Officer. "Our optimism continues to rise as these proof-of-concept data demonstrate a well-tolerated safety profile and strong NK cell activation against a broad range of tumors. In total, the Company’s TriKE nanobody platform, a rich platform technology, has demonstrated broad utility. We are confident in our ability to develop these assets as a monotherapy, as a combination therapy with conventional chemotherapy, or in combination with other potential joint commercialization technologies."

Quarterly Highlights
The Company presented pre-clinical TriKE data in an oral poster-presentation both virtually and in-person at ESMO (Free ESMO Whitepaper) Targeted Anticancer Therapies (TAT) Congress, March 7–8, 2022.
The pre-clinical evidence suggests, despite the difference in circulating immune cells of Stage IVB NSCLC patients, mesothelin-targeted TriKE can work alongside current standard of care and provide benefit even in the hypoxic environment of a solid tumor.
Dr. Jeffrey Miller, GT Biopharma consultant Chief Scientific Officer, also participated in an oral poster-presentation session at the European Society for Medical Oncology Immuno-Oncology (ESMO IO) Congress, December 8–11, 2021.
The presentation highlighted the broad activity of GTB-5550, which harbors wild-type IL-15 in combination with TriKE against B7-H3-expressing tumors.
Upcoming Conference Participation
GT Biopharma will participate in poster-presentation sessions at the following upcoming medical conferences:
EBMT Abstract AS_EBMT-2022-00508, "A Tri-specific Killer Engager (TriKE) against B7-H3 enhances NK cell mediated killing of multiple myeloma"
AACR Abstract 3435, "GTB-5550 (cam16-IL15-camB7H3) Tri-specific Killer Engager (TriKE) drives natural killer cell activation and antibody dependent cellular cytotoxicity against head and neck squamous cell carcinomas"
Fourth Quarter and Year End 2021 Financial Summary
Cash Position: The Company had total cash, cash equivalents and short-term investments of $32.0 million as of December 31, 2021, compared to $5.3 million as of December 30, 2020. This is expected to provide ample runway to fund operations into 2023 including Phase 1 clinical development of its lead products GTB-3650 and GTB-5550.

Research and Development (R&D) Expenses: R&D expenses for the fourth quarter of 2021 were $6.3 million compared to $233,000 in the same quarter a year ago. R&D expenses for the year-ending December 31, 2021, were $9.6 million compared to $485,000 in the year ended December 31, 2020. Research and development expenses increased primarily due to the admittance of additional patients into the Phase 1 GTB-3550 clinical trial and the continued development and production of our most advanced TriKE product candidates GTB-3650 and GTB-5550.

General and Administrative (G&A) Expenses: G&A expenses for the fourth quarter of 2021 were $11.8 million compared to $2.0 million in the same quarter a year-ago. G&A expenses for the year ending December 31, 2021, were $47.9 million compared to $6.3 million for the year ending December 31, 2020. The increase in general and administrative expenses was primarily attributable to the increase in stock-based compensation and expenses incurred in support of our planned growth and new public company compliance initiatives. For the year ended December 31, 2021, we incurred $33.9 million of stock-based compensation expense as compared to $269,000 in stock-based compensation expense for the year ended December 31, 2020.

Net Loss: For the fourth quarter of 2021, the Company reported a net loss of $18.0 million, compared to a net loss of $6.3 million in the same quarter a year ago. For the year ended December 31, 2021, the Company reported a net loss of $58.0 million compared to a net loss of $28.3 million for the year ending December 31, 2020.

About Camelid Antibodies
Camelid antibodies are single domain antibodies (sdAbs) from the Camelidae family of mammals that include llamas, camels, and alpacas. These animals produce two main types of antibodies. One type of antibody camelids produce is the conventional antibody that is made up of two heavy chains and two light chains. They also produce another type of antibody that is made up of only two heavy chains and no light chain. This is known as heavy chain IgG (hcIgG). While these antibodies do not contain the CH1 region, they retain an antigen binding domain called the VHH region. VHH antibodies, also known as single domain antibodies, contain only the VHH region from the camelid antibody. Camelid antibodies have key characteristics, which include high affinity and specificity (equivalent to conventional antibodies), high thermostability, good solubility and strictly monomeric behavior, small size, relatively low production cost, ease of genetic engineering, format flexibility or modularity, low immunogenicity, and a higher penetration rate into tissues.

On March 28, 2022 Everest Medicines (HKEX 1952.HK, "Everest", or the "Company"), a biopharmaceutical company focused on developing and commercializing transformative pharmaceutical products to address critical unmet needs in Asia Pacific markets, reported its financial results for full year ended December 31, 2021, along with a corporate progress update (Press release, Everest Medicines, MAR 28, 2022, View Source [SID1234611070]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Despite a challenging backdrop for the biopharmaceutical industry in 2021, we propelled the Company forward by achieving an impressive number of accomplishments across our business, including fostering key strategic partnerships, expanding its global presence by building teams in South Korea, Singapore, and the Taiwan region, receiving the first of several expected drug approvals for Trodelvy in Singapore and investing in COVID-19 vaccines and therapeutic candidates to address the world’s ongoing public health crisis," said Kerry Blanchard, MD, PhD, Chief Executive Officer of Everest Medicines.

"As 2022 progresses, we look forward to building on the momentum established last year to position our company for sustained future growth. We will persist in growing our clinical capabilities, pursuing our global expansion strategy and building a commercial-ready biopharmaceutical company in order to provide innovative medicines to patients in need. We will strive to accomplish these goals, committed as always to the highest standards of quality and integrity," said Blanchard.

Recent Product Highlights and Anticipated Milestones

Sacituzumab govitecan-hziy (Trodelvy), our anchor drug candidate in the oncology therapeutic area, is a first-in-class TROP-2 directed antibody-drug conjugate (ADC).

Clinical and regulatory development achievements during the Reporting Period:

– In January 2021, we submitted a New Drug Application ("NDA") to the Health Sciences Authority ("HSA") of Singapore for sacituzumab govitecan for the treatment of patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease, and the indication was subsequently amended to second-line and later lines metastatic TNBC.
– In January 2021, the Center of Drug Evaluation ("CDE") of the China National Medical Products Administration ("NMPA") approved a China clinical trial application ("CTA") for sacituzumab govitecan for the treatment of patients with metastatic urothelial cancer ("mUC").

– In March 2021, the CDE of the China NMPA approved a CTA for a phase 2 basket trial for a variety of cancers with high TROP-2 expression. The trial is designed to evaluate sacituzumab govitecan monotherapy in 180 patients with relapse/refractory esophageal squamous cell carcinoma, gastric cancer, and cervical cancer at select sites in China.

– In April 2021, the Company’s partner, Gilead Sciences, Inc. (Gilead), received full approval from the US FDA for Trodelvy for the treatment of adult patients with second-line metastatic triple-negative breast cancer (mTNBC).

– In April 2021, Gilead received accelerated approval from the US FDA for Trodelvy for the treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC) who have previously received a platinum-containing chemotherapy and either a programmed death receptor-1 (PD-1) or a programmed death-ligand 1 (PD-L1) inhibitor.

– In May 2021, NMPA accepted the Biologics License Application ("BLA") for sacituzumab govitecan for the treatment of second-line and later lines metastatic TNBC in adult patients. Following the BLA acceptance, sacituzumab govitecan was granted priority review by the CDE of China NMPA in May 2021.

– In May 2021, the Ministry of Food and Drug Safety ("MFDS") of South Korea had granted Fast Track Designation and Orphan Drug Designation to sacituzumab govitecan for the treatment of later line metastatic TNBC.

– In July 2021, Taiwan Food and Drug Administration ("TDFA") granted Pediatric and Rare Severe Disease Priority Review Designation for adult patients with second-line metastatic TNBC.

– In November 2021, the Company announced the topline results of its bridging study, EVER-132-001, a single-arm, multi-center Phase 2b study of sacituzumab govitecan conducted in China on patients with unresectable locally advanced or metastatic TNBC who have received two or more prior systemic therapies, at least one for metastatic disease.

– In December 2021, MFDS of South Korea accepted the Company’s NDA for sacituzumab govitecan for the treatment of second-line and later lines metastatic TNBC in adult patients.

– In December 2021, TFDA accepted the NDA submission of sacituzumab govitecan for the treatment of second-line and later lines metastatic TNBC in adult patients.

– The phase 3 Asia study was ongoing, which is designed to assess and compare the efficacy and safety of sacituzumab govitecan versus treatment of physician’s choice in Asian patients with hormone receptor positive, HER2 negative metastatic breast cancer ("HR+/HER2- mBC") who have failed at least two prior chemotherapy regimens. The trial will enroll approximately 330 HR+/HER2- mBC patients in Greater China and South Korea. The enrollment of this study is expected to complete enrollment by the first half of 2022.

Post-Reporting Period milestones and expected achievements:
– In January 2022, the Company announced it will participate in a study pursuant to a clinical trial collaboration between Gilead and Merck & Co., Inc. (MSD) to evaluate the combination of sacituzumab govitecan and MSD’s anti-PD-1 therapy Keytruda (pembrolizumab) in first-line metastatic non-small cell lung cancer (NSCLC).

– In January 2022, the HSA of Singapore approved the Company’s NDA for sacituzumab govitecan for the treatment of second-line and later lines metastatic TNBC.

– In March 2022, our partner Gilead announced results from the Phase 3 TROPiCS-02 study evaluating Trodelvy in patients with HR+/HER2- mBC who received prior endocrine therapy, CDK4/6 inhibitors and two to four lines of chemotherapy. The study met its primary endpoint with a statistically significant improvement in progression-free survival versus physician’s choice of chemotherapy.

– We anticipate receiving the BLA decision from China NMPA and NDA decision from the TDFA for sacituzumab govitecan for the treatment of second-line metastatic TNBC in 2022.

Nefecon (TARPEYO), our anchor drug candidate in cardio-renal therapeutic area, is a novel oral formulation of budesonide (budesonide delayed release capsules) in the development for the treatment of primary immunoglobulin A nephropathy ("IgAN").

Clinical and regulatory development achievements during the Reporting Period:
– The Company completed the Chinese patient enrollment into the NefIgArd Phase 3 global registrational study evaluating NEFECON as a treatment for primary IgAN.

– Our partner Calliditas Therapeutics AB, ("Calliditas") in April, 2021 granted an accelerated assessment procedure on its marketing authorization application ("MAA") for Nefecon in IgAN and submitted the MAA in May of 2021. In September 2021, Calliditas announced that the European Medicine Agency’s ("EMA") Committee for Human Medicinal Products ("CHMP") has decided to continue the assessment of the MAA for Nefecon under standard procedure assessment timelines, with potential conditional approval in second quarter of 2022.

– In December 2021, our partner Calliditas, announced that the US FDA approved TARPEYO (developed under Project name NEFECON) delayed release capsules the first and only treatment indicated to reduce proteinuria in adults with primary IgAN at risk of rapid disease progression.

Post-Reporting Period milestones and expected achievements:
– In March 2022, the Company entered into a license agreement with Calliditas to develop and commercialize NEFECON for the treatment of primary IgAN in South Korea, expanding its license in addition to rights held in Greater China and Singapore.

– We expect to conduct an interim analysis of the Chinese patients in the global phase 3 NefIgArd study and this is expected to lead to a regulatory submission in China in second half of 2022.

PTX-COVID19-B, a potentially best-in-class lipid nanoparticle-formulated mRNA COVID-19 vaccine with a strong immunogenicity and tolerability profile.

Clinical and regulatory development achievements during the Reporting Period:
– In December 2021, we announced jointly with Providence Therapeutics ("Providence") that scientists from both companies had analyzed the sequence of the SARS-CoV-2 Omicron variant, selected viral sequences and designed plasmid clones to develop a new version of the COVID-19 vaccine specifically targeting the new Omicron variant.

– In December 2021, PTX-COVID19-B was selected to be part of a World Health Organization (WHO) Solidarity Trial Vaccines (STV) clinical trial, an international, randomized clinical trial designed to rapidly evaluate the efficacy and safety of promising new candidate vaccines.

Post-Reporting Period milestones and expected achievements:
– Providence will readout the data for the phase 2 trial of PTX-COVID19-B around mid-2022 and initiate a phase 3 trial for booster indication in mid-2022 as well.

Eravacycline (Xerava), is a novel, fully synthetic fluorocycline intravenous antibiotic developed for use as first-line empiric monotherapy for the treatment of multidrug resistant (MDR) infections, including MDR Gram-negative infections.

Clinical and regulatory development achievements during the Reporting Period:
– In March 2021 and September 2021 respectively, the China NMPA and the Department of Health of Hong Kong accepted an NDA for eravacycline for the treatment of complicated intra-abdominal infections (cIAI).

– In August 2021, the CDE of the China NMPA approved the CTA for eravacycline for the treatment of community-acquired bacterial pneumonia (CABP).

Post-Reporting Period milestones and expected achievements:
– We expect NDA approval for eravacycline for the treatment in cIAI in China within 2022.

Other clinical-stage assets

Clinical and regulatory development achievements during the Reporting Period:
– In August 2021, the Phase 1b/2 study evaluating FGF401 in combination with PD-1 inhibitor, pembrolizumab, in patients with advanced solid tumors, such as hepatocellular carcinoma (HCC) reached recommended Phase 2 dose. The trial is ongoing.

– In September 2021, we received the approval from the CDE of the China NMPA for the Investigational New Drug application under the Class One category for SPR206 (also known as EVER206), a novel, intravenous next-generation polymyxin product candidate in development for the treatment of MDR Gram-negative bacterial infections.

– Ralinepag is a potentially best-in-class oral, selective potent, once-daily IP receptor agonist intended for the treatment of pulmonary arterial hypertension (PAH). We continue to progress our Phase 3 registrational trial for PAH in China as part of a global Phase 3 study conducted together with our partner United Therapeutics.

Post-Reporting Period milestones and expected achievements:
– In March 2022, our licensing partner, Venatorx Pharmaceuticals, reported positive results from its pivotal Phase 3 study, CERTAIN-1, evaluating cefepime-taniborbactam, an investigational new drug, versus meropenem as a potential treatment for hospitalized adult patients with complicated urinary tract infections (cUTI), including acute pyelonephritis.

– In March, our partner, Pfizer Inc. announced positive topline results from a phase 3 study of etrasimod in development for the treatment of moderately to severly active ulcerative colitis ("UC") patients. These data along with results from ELEVATE 52 are expected to form the basis for planned future regulatory filings. Results from the ELEVATE 52 study will be available by the end of first quarter.

– We are conducting a Phase 3 study for etrasimod for the treatment of moderately to severely active UC, which is expected to complete enrollment in 2023.

– We anticipate initiating the Phase 1b/2 trial of the EVER-001 (also known as XNW1011), a next-generation covalent reversible Bruton’s tyrosine kinase (BTK) inhibitor for the treatment of renal diseases in 2022.

– We expect Phase 1 clinical trials of EDDC-2214, as oral antiviral treatment against SAR-CoV-2 and its variants, to commence by the end of 2022.

Key Corporate Developments

On 18 February 2021, we appointed Kevin Guo as our chief commercial officer. Mr. Guo has more than 22 years of commercial leadership and business management experience across a number of multinational pharmaceutical companies. Under Mr. Guo’s leadership, we continue to remain focused on advancing our work across four strategic pillars to launch strategy formulation, develop commercial capabilities, embrace and deploy innovative solutions, and expand our international footprint.
Effective 15 March 2021, the Company was selected as a constituent stock of the Hang Seng Composite Index, the Hang Seng Healthcare Index and the Hang Seng Hong Kong-Listed Biotech Index in accordance with the latest index series release by Hang Seng Indexed Company Limited. At the same time, the Company became eligible for Southbound Trading under the Stock Connect Scheme, which is a channel that facilitates stock trading and investment between Hong Kong and a broader base of Chinese investors.
On 15 April 2021, we appointed Dr. Jennifer Yang as our chief scientific officer, whose deep expertise in drug discovery and translational medicine will help the Company establish a robust discovery organization that contributes to the strategic expansion of our clinical development pipeline.
Effective 18 June 2021, the Company’s stock was included as a constituent stock of the Small Cap Index, FTSE All-Cap Index and FTSE Total-Cap Index in the FTSE Global Equity Index Series.
Effective 30 November 2021, the Company’s stock was added to the MSCI Global Small Cap Indexes — MSCI China Index.
Business Development Updates

In July 2021, the Company established key strategic partnerships with Tencent Holdings Limited (Tencent), Medbanks Health Technology Co., Ltd (Medbanks) and MediTrust Health Co., Ltd. (MediTrust) to explore innovative tools in digital marketing, patients’ access to novel medicines and payment solutions. In January 2022, the Company announced a strategic commercialization cooperation with Yuanxin Group and a strategic cooperation with the Sinopharm Group ("Sinopharm").
In September 2021, the Company entered into two separate definitive agreements with Providence, a clinical stage biotechnology company developing mRNA therapeutics and vaccines, to (i) license rights to Providence’s mRNA COVID-19 vaccine candidates in Asia’s emerging markets, including Greater China, Southeast Asia and Pakistan, and (ii) establish a broad, strategic partnership to develop mRNA products globally leveraging Providence’s cutting-edge mRNA technology platform.
In September 2021, we entered into an exclusive licensing agreement with Sinovent and SinoMab to develop, produce and commercialize EVER-001 (also known as XNW1011), a covalent reversible BTK inhibitor, globally for the treatment of renal diseases.
In September 2021, we announced a multi-year collaboration and license agreement with AbCellera Biologics Inc. (AbCellera) to discover therapeutic antibodies for up to 10 targets selected by the Company. The partnership will help to expand Company’s portfolio of novel medicines across multiple indications, with the initial programs focusing on targets in oncology and the renal space.
In January 2022, we entered into a global licensing agreement with Singapore’s national platform for drug discovery and development, the EDDC for the exclusive worldwide rights to develop, manufacture and commercialize EDDC’s series of viral 3C-like (3CL) protease inhibitors as a potentially best-in-class oral antiviral treatment against SARS-CoV-2 and its variants. The Company has full rights to sub-license the drug further and will receive a full technology transfer.
Financial Highlights

IFRS Numbers:

Research and development ("R&D") expenses increased by RMB236.0 million to RMB613.4 million for the year ended 31 December 2021, from RMB377.4 million for the year ended 31 December 2020, primarily due to: (i) increased number of clinical trials for our drug candidates; (ii) expansion of internal discovery team to build up in-house R&D capabilities; and (iii) increased costs occurred in the process of technical transfer for our drug candidates.
General and administrative expenses decreased by RMB35.1 million to RMB242.7 million for the year ended 31 December 2021, from RMB277.8 million for the year ended 31 December 2020, primarily due to decreased expenses in relation to the public listing of the Company in 2020.
Distribution and selling expenses increased by RMB165.0 million to RMB198.2 million for the year ended 31 December 2021, from RMB33.2 million for the year ended 31 December 2020, primarily due to expansion of commercial organization and pre-launch and launch activities carried out for product commercialization.
Net loss for the year ended 31 December 2021 was RMB1,008.7 million, from RMB5,658.2 million for the year ended 31 December 2020, primarily attributable to the decrease in loss from fair value change in financial instruments issued to investors.
Cash and cash equivalents amounted to RMB2,640.1 million as of 31 December 2021
Non-IFRS Measure

Adjusted loss for the year[1] was RMB777.3 million for the year ended 31 December 2021, representing an increase of RMB174.4 million from RMB602.9 million for the year ended 31 December 2020, primarily due to increase in R&D expense and distribution and selling expenses.
Conference Call Information

A live conference call will be hosted on March 29, 2022 at 9:00 AM Beijing Time (March 28, 2022 at 9:00 PM U.S. Eastern Time).

The live webcast of the conference call will be available at View Source

Alternatively, participants may dial in to the conference call using below dial-in information:

A replay will be available shortly after the call and can be accessed by visiting the Company’s website at View Source

On March 28, 2022 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, metabolic, autoimmune and other major diseases, reported the first patient dosing for its proprietary recombinant bispecific antibody targeting Claudin18.2 and CD3 (R&D code: IBI389) in a Phase I clinical trial for the treatment of advanced malignancies (Press release, Innovent Biologics, MAR 28, 2022, View Source [SID1234611069]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The study (NCT05164458) is an open, multicenter Phase 1a/1b study evaluating the safety, tolerability and efficacy of IBI389 monotherapy or combination therapy in the treatment of advanced solid tumors.

CD3-targeted bispecific antibodies (CD3-BsAbs) or T Cell Engager (TCE) are emerging novel therapeutic modalities in cancer immunotherapy in recent years. TCE redirects T cells to tumor cells by simultaneously binding tumor-associated antigen (TAA) expressed on tumor cells and CD3 expressed on T cells, thus inducing T cell killing of tumor cells. Differentiated from conventional immunotherapies, CD3-BsAbs provoke a stronger immune response through CD3-activated T cells without the binding of the T cell receptor (TCR) to the major histocompatibility complex (MHC)-peptide complex, and also do not rely on T cell-activated co-stimulatory signals.IBI389 has the potential to efficiently and selectively kill CLDN18.2-expressing tumor cells, increasing lymphocytic tumor infiltration and enhancing tumor immune response, while possessing a low risk of CRS (cytokine release syndrome). Preclinical results showed that IBI389 exhibited significant antitumor effects and could bound to tumor cells even in cell lines with low CLDN18.2 expression, and is promising to treat patient populations with low to moderate CLDN18.2 expression where conventional antibodies are found limited response.

The principal investigator of the study, Professor Feng Bi, Director of the Department of Abdominal Oncology and Director of the Molecular Targeted Therapy Research Unit at West China Hospital of Sichuan University, pointed out: "In recent years, CLDN18.2 has become one of the most topical R&D areas in molecular biology, and preliminary efficacy results in some clinical studies demonstrated encouraging druggablity of this target. IBI389 bispecific antibody distinguishes itself from traditional monoclonal antibodies by encouraging T-cell infiltration and killing of tumors, thus enhancing the antitumor effect as a single agent. We are looking forward to the positive results of IBI389 in patients with CLDN18.2-expressing solid tumors."

Dr. Hui Zhou, Senior Vice President of Innovent, said: " IBI389 marks an exciting start for Innovent in the TCE field. The scientists of Innovent Academy has accomplished sophisticated research, screen and design work in drug discovery stage, and the results of preclinical studies show that IBI389 has a potent anti-tumor effect with a good safety profile. We believe that as a differentiated molecule targeting CLDN18.2, IBI389 will bring benefits to patients with advanced gastric cancer and pancreatic cancer even with low CLDN18.2 expression."

About IBI389

IBI389 is an anti-CLDN18.2/CD3 bispecific antibody discovered and developed by Innovent. It induces immune synapse formations by linking CD3 molecules in T-cell receptor complexes and CLDN18.2 antigens on the surfaces of tumor cells. Therefore IBI389 stimulates T-cell activation, resulting in cytolytic protein production, inflammatory cytokine release and further T-cell proliferation, which eventually leads to durable anti-tumor effects.

About Claudin 18.2

Claudin protein is a critical component of tight junction complex molecules which play an important role in the life activities of the human body. Claudin18.2 is a member of the Claudin protein family, which is a highly tissue-specific protein expressed only in differentiated epithelial cells on the gastric mucosa under normal physiological conditions. Previous studies have revealed that Claudin18.2 is highly expressed in multiple types of cancer such as gastric cancer, pancreatic cancer, esophageal adenocarcinoma, and colorectalcancer. The unique feature of limited expression in normal tissues and highly specific expression in cancer makes Claudin18.2 an ideal target for developing the immunotherapeutic for solid tumors. Globally, there are many candidate therapies in clinical development. The drug modalities under development include monoclonal antibodies, bispecific antibodies, antibody-conjugated drugs and CAR-T cell products. However, currently no drug targeting Claudin18.2 has been approved.

About Gastric and Pancreatic adenocarcinoma

Gastric and pancreatic cancer are both malignant tumors of the digestive system that seriously endanger human life and health. The latest global cancer statistics show that there will be about 1.089 million new cases of gastric cancer worldwide in 2020, accounting for 5.6% of the global cancer incidence, and about 768,000 deaths, accounting for 7.7% of the global cancer deaths. There are about 495,000 new cases of pancreatic cancer, accounting for 2.6% of the global cancer incidence, and about 466,000 deaths, accounting for 4.7% of the global cancer deaths. According to the national cancer statistics released by the National Cancer Center of China in 2019, the incidence of gastric cancer in China in 2015 was about 403,000, accounting for 10.26% of the total cancer incidence, second only to lung cancer at 20.03%, with an incidence rate of 29.31/100,000 people, and about 291,000 deaths, accounting for 12.45% of the total cancer deaths, behind lung and liver cancer, with a mortality rate of 21.16/100,000 people. In 2015, the number of cases and deaths of pancreatic cancer nationwide were 95,000 and 85,000 respectively, ranking the 10th and 6th in the incidence and mortality of malignant tumors. The mortality ratio of pancreatic cancer was 0.89, making it a true "King of Cancer". Despite the treatment progress in recent years, drug resistance, recurrence and metastasis are still inevitable. The 5-year survival rate of patients with advanced gastric cancer is about 5-20%, and the median survival rate is about 10 months. Pancreatic cancer has a worse prognosis, with a 5-year survival rate of only 6 to 8%.

On March 28, 2022 Lucid Diagnostics Inc. (Nasdaq: LUCD) ("Lucid", the "Company") a commercial-stage, cancer prevention medical diagnostics company, and majority-owned subsidiary of PAVmed Inc. (Nasdaq: PAVM, PAVMZ) ("PAVmed"), reported a business update for the company and presented preliminary financial results for the year ended December 2021 (Press release, Lucid Diagnostics, MAR 28, 2022, View Source [SID1234611068]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Conference Call and Webcast

A conference call and webcast for today’s business update and fourth quarter and year ended December 31, 2021, financial results will take place at 4:30 PM EDT. To access the conference call, listeners should dial 877-407-0789 toll-free in the U.S. or 201-689-8562 and ask to join the "Lucid Diagnostics Business Update Conference Call". The conference call will be available live via a webcast and for replay at the investor relations section of the Company’s website at www.luciddx.com. Following the conclusion of the conference call, a replay will be available for one week and can be accessed by dialing 844-512-2921 toll-free in the U.S. or 412-317-6671, followed by the PIN number: 13727145.

Business Update Highlights

"I am happy to report that Lucid Diagnostics is firing on all cylinders," said Lishan Aklog, M.D., Lucid’s Chairman and Chief Executive Officer. "Our rapidly growing team is making excellent progress on all fronts and is laying a solid foundation for us to continue driving our long-term growth strategy. This includes EsoGuard commercialization, the rollout of our Lucid Test Center network, expansion of our sales infrastructure and operations, our laboratory operations, and clinical trial work. Our strong balance sheet provides us with the resources to execute on this strategy."

The Company reported solid EsoGuard commercialization progress with excellent traction and robust growth in EsoGuard testing volume. Lucid processed 303 commercial EsoGuard tests in the fourth quarter of 2021, which represents an approximately 50% increase sequentially from the third quarter and a nearly 200% increase annually from the fourth quarter of 2020. This growth has continued into the new year, both in referrals to Lucid Test Centers and tests performed at gastroenterology and foregut surgeon practices.
The Lucid Test Center program has completed its first stage, having advanced from a pilot program in Phoenix, launched in the third quarter of 2021, to a regional Southwest and Pacific Northwest program also covering Denver, Salt Lake City, Las Vegas, Seattle, Portland, and Boise. The Company reported that its experience with the test centers over the past six months has validated the test center model as a key driver of EsoGuard testing volume by simplifying the engagement of its sales reps with primary care physicians. Lucid is now in the process of launching the next stage of its Lucid Test Center program, with accelerated expansion into larger states across the nation. It has hired an experienced Director or Clinical Services who will oversee this expansion. The Company is also continuing the pilot of its EsoGuard Telemedicine Program, operated in partnership with independent third-party telemedicine provider UpScript, which launched in December 2021. It has pursued a direct-to-consumer advertising program on a limited pilot basis in Phoenix.
The Company reported significant expansion of its sales infrastructure and operations during the fourth quarter and recent months. The team, led by its national VP of sales, now consists of three area directors covering the East, Central and West respectively, six market development managers, ten sales representatives, and several sales operations staff. The company expects the overall sales team to double in size and the number of sales reps to triple by the end of the calendar year. The company also reported substantial progress in honing its data and analytics driven sales process and intensive sales training to drive commercial success.
Last month the Company announced that LucidDx Labs, a wholly-owned subsidiary of Lucid, had acquired certain licenses and other related assets from its long time CLIA laboratory partner, Research Dx, which allowed it to operate own new CLIA-certified, CAP-accredited clinical laboratory in Lake Forest, CA. The Laboratory has completed the necessary assay validations to process clinical samples as a Laboratory Developed Test (LDT), completed a College of American Pathologists (CAP) audit, and begun performing EsoGuard testing at the new facility.
In conjunction with it taking over the laboratory and fully controlling the EsoGuard billings and collection process, the Company has been able to upgrade our revenue cycle management provider and simplify the billing and collections process it had to utilize as a partner of a third-party commercial laboratory. It is now in position to start submitting Medicare claims using the effective $1938 Medicare payment rate. The Company continues to wait for Medicare Administrative Contractor Palmetto GBA’s MolDx program to issue a draft local coverage determination (LCD) following an encouraging Contractor Advisory Committee (CAC) meeting in the fall.
The laboratory has been submitting claims to private payors and is encouraged that it has been receiving approximately $1,150 per test representing approximately 60% out-of-network coverage. It reported that is reaching critical threshold of submitted and processed claims in certain locales which will allow it to begin having meaningful conversations with select private payors in these locales on in-network payment and coverage. It is expanding its market access team and collecting the critical clinical utility data to allow it to fully engage in these negotiations.
In March 2022, both the PAVmed and Lucid board of directors approved entering into an intercompany license between PAVmed and Lucid such that Lucid will be granted the rights to commercialize EsoCure for the endoscopic treatment of late esophageal precancer (dysplastic Barrett’s Esophagus), including a royalty arrangement whereby Lucid will pay PAVmed a 5% royalty on all EsoCure sales up to $100 million per calendar year, and 8% above that threshold.
In March 2022, both the PAVmed and Lucid board of directors approved entering into a purchase and sale of the CapNostics, LLC assets, including the EsophaCap non-endoscopic sponge-based esophageal cell collection device, from PAVmed to Lucid as well as transferring the consulting agreement with the principal owner of CapNostics, LLC prior to the purchase by PAVmed on October 5, 2021.
Preliminary Financial Results

For the fourth quarter of 2021, EsoGuard related revenues were $0.3 million, while for the year ended December 31, 2021, revenues were $0.5 million. Fourth-quarter and full-year 2021 operating expenses were approximately $11.1 million and $27.3 million, respectively, which include stock-based compensation expenses of $3.2 million and $9.6 million, respectively. GAAP net loss attributable to common stockholders for the fourth quarter and full-year 2021 were approximately $11.3 million and $28.1 million, or $(0.32) and $(1.51) per common share.
As shown below and for the purpose of illustrating the effect of stock-based compensation and other non-cash income and expenses on the Company’s financial results, the Company’s preliminary non-GAAP adjusted loss for the fourth quarter and year ended December 31, 2021, were approximately $7.7 million and $17.8 million or $(0.22) and $(0.96) per common share.
Lucid had cash and cash equivalents of $53.7 million as of December 31, 2021, compared to $0.1 million as of December 31, 2020.
On March 28, 2022, the Company entered into a Common Stock Purchase Agreement (the "Purchase Agreement") with CF Principal Investments LLC ("Cantor"), an affiliate of Cantor Fitzgerald, relating to a committed equity facility (the "Facility"). Pursuant to the Purchase Agreement, the Company has the right to sell to Cantor up to $50.0 million of its common shares (the "Shares"), subject to certain conditions and limitations set forth in the Purchase Agreement. While there are distinct differences, the Facility is structured similarly to a traditional at-the-market equity facility, insofar as it allows the Company to raise primary equity capital on a periodic basis at a price related to the current market price.
Sales of the Shares to Cantor under the Purchase Agreement, and the timing of any sales, will be determined by the Company from time to time at its sole discretion and will depend on a variety of factors, including, among other things, market conditions, the trading price of the Shares and determinations by the Company regarding the use of proceeds of such Shares. Upon the satisfaction of the conditions to Cantor’s obligation to purchase Shares, the Company will have the right, from time to time during the 36-month period after the commencement of the Facility, to direct Cantor to purchase up to a maximum number of Shares on any trading day. The purchase price of the Shares will be 96% of the volume-weighted average price of the Shares on such trading day.
The unaudited financial results for the year ended December 31, 2021, will be filed with the SEC on Form 10-K in the coming days and will be available at www.luciddx.com or www.sec.gov.
Lucid Non-GAAP Measures

To supplement our unaudited financial results presented in accordance with U.S. generally accepted accounting principles (GAAP), management provides certain non-GAAP financial measures of the Company’s financial results. These non-GAAP financial measures include net loss before interest, taxes, depreciation, and amortization (EBITDA), and non-GAAP adjusted loss, which further adjusts EBITDA for stock-based compensation expense and other non-cash income and expenses, if any. The foregoing non-GAAP financial measures of EBITDA and non-GAAP adjusted loss are not recognized terms under U.S. GAAP.
Non-GAAP financial measures are presented with the intent of providing greater transparency to the information used by us in our financial performance analysis and operational decision-making. We believe these non-GAAP financial measures provide meaningful information to assist investors, shareholders, and other readers of our unaudited financial statements in making comparisons to our historical financial results and analyzing the underlying performance of our results of operations. These non-GAAP financial measures are not intended to be, and should not be, a substitute for, considered superior to, considered separately from or as an alternative to, the most directly comparable GAAP financial measures.
Non-GAAP financial measures are provided to enhance readers’ overall understanding of our current financial results and to provide further information for comparative purposes. Management believes the non-GAAP financial measures provide useful information to management and investors by isolating certain expenses, gains, and losses that may not be indicative of our core operating results and business outlook. Specifically, the non-GAAP financial measures include non-GAAP adjusted loss, and its presentation is intended to help the reader understand the effect of the loss on the issuance or modification of convertible securities, the periodic change in fair value of convertible securities, the loss on debt extinguishment, and the corresponding accounting for non-cash charges on financial performance. In addition, management believes non-GAAP financial measures enhance the comparability of results against prior periods.
A reconciliation to the most directly comparable GAAP measure of all non-GAAP financial measures included in this press release for the fourth quarter and year ended December 31, 2021, and 2020 is as follows

About EsoGuard and EsoCheck

Millions of patients with GERD are at risk of developing esophageal precancer and a highly lethal form of esophageal cancer ("EAC"). Over 80% of EAC patients die within five years of diagnosis, making it the second most lethal cancer in the U.S. The mortality rate is high even in those diagnosed with early stage EAC. The U.S. incidence of EAC has increased 500% over the past four decades, while the incidences of other common cancers have declined or remained flat. In nearly all cases, EAC silently progresses until it manifests itself with new symptoms of advanced disease. All EAC is believed to arise from esophageal precancer, which occurs in approximately 5% to 15% of at-risk GERD patients. Early esophageal precancer can be monitored for progression to late esophageal precancer which can be cured with endoscopic esophageal ablation, reliably halting progression to cancer.

Esophageal precancer screening is already recommended by clinical practice guidelines in millions of GERD patients with multiple risk factors, including age over 50 years, male gender, White race, obesity, smoking history, and a family history of esophageal precancer or cancer. Unfortunately, fewer than 10% of those recommended for screening undergo traditional invasive endoscopic screening. The profound tragedy of an EAC diagnosis is that likely death could have been prevented if the at-risk GERD patient had been screened and then undergone surveillance and curative treatment.

The only missing element for a viable esophageal cancer prevention program has been the lack of a widespread screening tool that can detect esophageal precancer. Lucid believes EsoGuard and EsoCheck are the missing element and constitute the first and only commercially available test capable of serving as a widespread screening tool to prevent esophageal cancer deaths through the early detection of esophageal precancer in at-risk GERD patients.

EsoGuard is a bisulfite-converted NGS DNA assay performed on surface esophageal cells collected with EsoCheck which quantifies methylation at 31 sites on two genes, Vimentin (VIM) and Cyclin A1 (CCNA1). The assay was evaluated in a 408-patient, multicenter, case-control study published in Science Translational Medicine and showed greater than 90% sensitivity and specificity at detecting esophageal precancer and cancer.

EsoCheck is an FDA 510(k) and CE Mark cleared noninvasive swallowable balloon capsule catheter device capable of sampling surface esophageal cells in a less than five-minute office procedure. It consists of a vitamin pill-sized rigid plastic capsule tethered to a thin silicone catheter from which a soft silicone balloon with textured ridges emerges to gently swab surface esophageal cells. When vacuum suction is applied, the balloon and sampled cells are pulled into the capsule, protecting them from contamination and dilution by cells outside of the targeted region during device withdrawal. Lucid believes this proprietary Collect+Protect technology makes EsoCheck the only noninvasive esophageal cell collection device capable of such anatomically targeted and protected sampling. The sample is sent by overnight express mail to Lucid’s third-party CLIA-certified laboratory partner for EsoGuard testing.