Thermo Fisher Scientific and AstraZeneca to Co-Develop NGS-based Companion Diagnostics

On September 1, 2021 Thermo Fisher Scientific’s clinical sequencing business and AstraZeneca reported they will co-develop next-generation sequencing (NGS)-based companion diagnostics (CDx) to support AstraZeneca’s expanding portfolio of targeted therapies (Press release, Thermo Fisher Scientific, SEP 1, 2021, View Source [SID1234587231]). The companies will collaborate under a multiyear, global agreement.

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"As the pipeline of targeted therapies expands, the availability of diagnostic tools that can interrogate multiple biomarkers simultaneously will ensure patients can be matched with the right therapies more rapidly – this is the promise of precision medicine," said Garret Hampton, president of clinical next-generation sequencing and oncology at Thermo Fisher Scientific. "Introduction of diagnostic tools early in the process of drug development can further facilitate the success of companion diagnostic development – and that’s what we’re doing with AstraZeneca."

NGS-based companion diagnostics are increasingly used to match patients with new therapies for cancer and other diseases. More than 90 percent of AstraZeneca’s clinical pipeline, across all main areas from oncology, cardiovascular and renal to metabolic and respiratory disease, are targeted precision medicine therapies.

"Using the latest diagnostic science allows us to match the best treatment to the patient," said Ruth March, senior vice president, precision medicine and biosamples, AstraZeneca. "This collaboration with Thermo Fisher offers the technology, expertise and ability to decentralize CDx tests to local healthcare providers across our global markets, which will help us identify more patients around the world who may benefit from treatments and effective patient care."

Thermo Fisher currently offers the only globally distributable NGS CDx solution approved and reimbursed by government and commercial insurers in more than 15 countries, including the U.S., multiple European nations, Japan, South Korea and the Middle East, and covering more than 550 million lives globally.

To expand global access to a growing list of precision medicine therapies, in 2019 Thermo Fisher introduced the Ion Torrent Genexus System*, the first fully-integrated NGS platform featuring an automated specimen-to-report workflow that economically delivers results in a single day. The company’s complete NGS workflow, powered by Ion AmpliSeq technology, includes multiple solutions for solid tumor biomarkers and liquid biopsy testing.

*Currently for Research Use Only. Not for use in diagnostic procedures.

Oasmia to present at Aktiedagen Stockholm on September 7

On August 31, 2021 Oasmia Pharmaceutical’s CEO, Dr Francois Martelet reported that it will present at Aktiespararna’s Aktiedagen Stockholm on September 7, 2021 (Press release, Oasmia, AUG 31, 2021, View Source [SID1234587041]). The presentation starts at 10:30 CEST and will be broadcast live as a webcast at: www.aktiespararna.se/tv/live.

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The presentation will be available online the following day on www.aktiespararna.se/tv/evenemang and on Oasmia Pharmaceutical’s website www.oasmia.com

Endevica Bio Reports TCMCB07 Preserves Lean Body Mass in Preclinical Cancer Cachexia Study

On August 31, 2021 Endevica Bio, a company developing best-in-class peptide drug candidates with better safety and efficacy properties, reported that new data from a recent preclinical study with its lead compound TCMCB07 at the 6th Cancer Cachexia Conference in August 27-29, 2021 (Press release, Endevica Bio, AUG 31, 2021, View Source [SID1234587058]). The study was conducted by researchers at Oregon Health & Science University. The results were presented in a poster titled "Melanocortin-4 receptor antagonist TCMCB07 preserves lean muscle mass during cancer cachexia."

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The researchers evaluated efficacy of TCMCB07 with subcutaneous administration in two recently developed mouse cachexia models of orthotopic pancreatic cancer and head and neck cancer. The data demonstrate that TCMCB07 can preserve lean mass as well as attenuate muscle wasting and body weight loss during cancer cachexia. The authors concluded that TCMCB07 is a promising drug candidate with universal effects on treating cancer cachexia.

TCMCB07 is a first-in-class melanocortin ¾ antagonist peptide designed to help people with cachexia to live longer by enabling greater tolerability of treatment and improved quality of life. Discovered by Endevica Bio founder and CEO, Dr. Kenneth Gruber, the compound reduces catabolism and energy expenditure via inhibiting the hypothalamic melanocortin signing and brain inflammation. TCMCB07 can effectively cross the blood-brain barrier when administering it peripherally.

"Even with only modest improvements in food intake in mouse cancer cachexia models, TCMCB07 significantly improves the maintenance of lean body mass," said Dr. Xinxia Zhu, Staff Scientist and the study lead investigator in the Marks Lab at Oregon Health & Science University "This is an important point because general appetite stimulants do not effectively ameliorate cachexia."

"Given that there are no approved drug therapies for cachexia in the United States, these data are incredibly promising and give us confidence that TCMCB07 may be effective as a treatment for cachexia caused by any type of cancer," said Russ Potterfield, Executive Chairman of Endevica Bio. "We are looking forward to studying TCMCB07 further and commencing clinical trials in the beginning of 2022."

Cachexia, a serious clinical consequence also known as "wasting syndrome," is estimated to be prevalent in approximately 50-80% of those with advanced cancer and it is estimated to be the cause of death for up to 40% of cancer patients.

Supporting Pelotonia’s goal to fund equitable cancer research

On August 31, 2021 Cardinal Health reported we’re passionate about giving back to the communities where we live and work, and we’re particularly committed to Pelotonia, an organization with a straight forward goal – end cancer (Press release, Cardinal Health, AUG 31, 2021, View Source [SID1234591441]). Our company has been a notable funding partner of Pelotonia since the organization’s inception in 2008. Each August, Pelotonia hosts a three-day experience that unites thousands of people in Central Ohio to bike, donate, volunteer, or cheer on the cyclists – all to raise awareness and life-saving funds for cancer research. Hundreds of our employees participate each year and, combined with contributions from Cardinal Health and our Foundation, have donated more than $3 million to Pelotonia.

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"As a cancer survivor, I’m very proud of the work Pelotonia drives to fund innovative research," said Victor Crawford, CEO of our Pharmaceutical segment, and member of the Pelotonia Board of Directors. "And, as a Black man, I share Pelotonia’s commitment to ensuring that research funding is equitably dispersed in order to address disparities in cancer care."

According to the research journal Nature Cancer, racial and ethnic "inequalities are prevalent across the spectrum of cancer research and patient care," and impact access to and quality of care, cancer prevention diagnoses and health outcomes. In America, Black and African Americans experience higher cancer death rates than Whites, according to the National Cancer Institute. And Black and African Americans and Native Americans are underrepresented in clinical trials, even when the drugs being tested are for cancers that disproportionately impact these populations, according to ProPublica.

Among Pelotonia’s key priorities are investing in cancer research initiatives designed to reduce health disparities, and forging a more inclusive path to research dollars for talented scientists from underrepresented populations in the medical community.

The COVID-19 pandemic has further exposed the disparities in cancer care around the world. That’s why Pelotonia has pledged $1 million to support research for COVID-19’s effect on the cancer community, including a research study to determine how COVID-19 impacts the immune system of cancer patients. The study, known as SIIREN (Study of Infections and Immune REspoNse), aims to advance the scientific community’s understanding of how effective the COVID-19 vaccine is for preventing COVID-19 infection, determine if the vaccine is less effective in cancer patients receiving certain therapies and determine how long the immunity lasts. (There is no peer reviewed published data available on how cancer therapy affects the vaccine’s efficacy because patients in active therapy were excluded from vaccine trials. However, it is widely recommended that all cancer patients be vaccinated.) Patients who are currently in treatment or have been treated for cancer at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) may qualify for the COVID-19 study. Learn more here.

Pelotonia is partnering with the American Cancer Society and Pfizer to help fund Turning the Page on Breast Cancer, an initiative designed to address the disparately high breast cancer death rates among Ohio’s African American women. The program will provide breast cancer risk assessment and facilitate adherence to appropriate screenings based on personal risk – including helping those women who are at greater risk access genetic counseling and recommended testing.

"Pelotonia is about raising money for equitable and pioneering research and lifesaving clinical trials," Crawford said. "I’m incredibly grateful for the part our organization plays in this mission and for the hundreds of Cardinal Health employees who support Pelotonia each year – helping to raise funds to improve cancer research for all."

All participant-raised funds go to cancer research at OSUCCC – James. The positive impact of that research is felt around the world. To learn more, or to make a donation, please visit pelotonia.org.

Top of page: Pelotonia CEO Doug Ulman (left) and Victor Crawford challenged each other to a stationary bike race during a mostly virtual Pelotonia kickoff earlier this year.

I-Mab Provides Business and Corporate Updates and Reports Financial Results for the Six Months Ended June 30, 2021

On August 31, 2021 I-Mab (the "Company") (Nasdaq: IMAB), a clinical stage biopharmaceutical company committed to the discovery, development and commercialization of novel biologics, reported financial results for the six months ended June 30, 2021, and provided key business updates (Press release, I-Mab Biopharma, AUG 31, 2021, View Source [SID1234587042]).

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During the reporting period, I-Mab has made remarkable progress in its key business areas. Firstly, on the R&D front, the Company has rapidly advanced its globally competitive pipeline and achieved all critical clinical milestones as set in early 2021 for the key pipeline assets. More specifically, the Company had seven clinical trials initiated or soon to be initiated, achieved five key data readout events for its differentiated investigational drugs, i.e. CD38 antibody felzartamab (TJ202/MOR202), CD47 antibody lemzoparlimab (TJC4), CD73 antibody uliledlimab (TJD5), GM-CSF antibody plonmarlimab (TJM2) and novel IL-6 inhibitor olamkicept (TJ301). Furthermore, the Company has made significant progress in expanding the current pipeline through the bi-specific antibody panel, where two lead assets have advanced to clinical trials in the U.S. in early 2021, as well as the next generation of novel antibody candidates enabled by transformative technologies through collaborations. In this regard, the Company has successfully entered into five technology partnering deals to gain access to cutting-edge technologies to generate novel drug molecules with uniquely acquired drug properties, including mRNA delivery, AI-guided targeting, cell-penetrating antibody and tumor-site activation. Secondly, on the corporate development front, the Company has met all expected corporate milestones with respect to building its manufacturing facility in Hangzhou and its commercialization capabilities and preparation of the market launch of felzartamab. I-Mab is now globally connected with six sites or offices in China and two R&D facilities in the U.S. Thirdly, during the reporting period, the Company has initiated its dual listing plan for the STAR Market in China and received multiple prestigious corporate honors by the global biotech community and the capital market. The Company also made efforts to further strengthen its Board of Directors and Scientific Advisory Board with internationally reputable experts.

"With the corporate focus and execution by our highly committed team, I-Mab has managed to have successfully delivered outstanding results that have exceeded our original expectations set early this year," said Dr. Jingwu Zang, Founder and Chairman of I-Mab. "We are thrilled by the achievements because many of the milestones are critical as they have provided positive and enabling clinical data needed for the further development of the key pipeline assets. Looking ahead, we will have 19 clinical trials either ongoing or soon to be initiated in both the United States and China by the end of this year, including our first BLA submission in Q4 2021. With these achievements, our pipeline is now not only innovative and globally competitive but also advanced with more assets moving towards late-stage clinical trials and BLA."

"The progress we have made so far has placed us firmly on track to deliver the rest of the critical milestones and has effectively secured our overall development plan for the key assets such as felzartamab, eftansomatropin alfa, lemzoparlimab, uliledlimab, and plonmarlimab. We are very excited and confident to succeed in our journey to transition from a clinical stage biotech now to a global biopharma within the next few years," Dr. Zang concluded.

Recent Pipeline Highlights and Upcoming Milestones

I-Mab has completed felzartamab 3L registrational trial, enabling the Company’s first BLA submission in Q4 2021, and currently manages two additional registrational trials, seven Phase 2 and eight Phase 1 clinical studies that are either ongoing or soon to be initiated in the U.S. and China. In parallel, a series of pre-clinical programs representing the next generation of innovative assets, i.e. bi-specific antibodies as well as so called "super antibodies", are under the development and some will advance towards IND application in 2022.

Rapidly Advancing Clinical Development of the Late-Stage Assets for Near-Term Value Creation

(1) Phase 3/pre-BLA assets

Felzartamab (TJ202/MOR202): A differentiated CD38 antibody for the treatment of multiple myeloma (MM) and potentially autoantibody-mediated autoimmune diseases such as systemic lupus erythematosus (SLE). I-Mab has licensed development, manufacturing and commercialization rights for felzartamab in Greater China from MorphoSys.

Felzartamab for MM third-line treatment is on track for BLA submission in Q4 2021 and MM second-line registrational trial is on track. The Company plans to submit a new IND application in Q3 2021 to explore the combination of felzartamab with another I-Mab clinical asset as a potential first-line treatment for MM. The rationale of this combination study is strongly supported by the pre-clinical evidence.

Third-line MM: The topline data of the registrational trial have met the primary and secondary endpoints. More importantly, the data have confirmed the clinical advantages of felzartamab with respect to its lower infusion-related reaction rate, shorter infusion time for out-patient administration etc. BLA submission is on track for Q4 2021. Under the leadership of Mr. Zhu, Chief Commercial Officer, the Company has assembled an integrated multi-functional team to focus on the launch readiness of felzartamab in China.
Second-line MM: Phase 3 registrational trial of felzartamab in combination with lenalidomide for second-line MM is on track. The Company expects to complete patient enrollment in September 2021. The topline data package is expected to support a BLA submission in 2023.
Potential first-line MM: A new IND application is planned in Q3 2021 to initiate a clinical trial for the combination of felzartamab with another I-Mab clinical asset as a potential first-line treatment for MM.
SLE: in June 2021, The Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) has approved the Company’s IND application to initiate Phase 1b trial of felzartamab in patients with SLE in Q4 2021.
Eftansomatropin alfa (TJ101): A differentiated long-acting growth hormone for pediatric growth hormone deficiency (PGHD). Eftansomatropin alfa is the only rhGH in its proprietary fusion protein format (pure protein-based molecule) and is not chemically linked with PEG or other linkers. Its safety, tolerability, and efficacy have been well demonstrated in a phase 2 clinical trial in the EU. I-Mab has the development, manufacturing, and commercial rights of eftansomatropin alfa in China from Genexine.

PGHD: in February 2021, the first patient was dosed in Phase 3 registrational trial (TALLER) of eftansomatropin alfa as a weekly treatment for PGHD patients in China. Complete patient enrollment (N=165) is expected in early 2022 to be on track for a planned BLA submission in 2023.
In parallel, the Company is under active discussions with potential commercial partners for the commercialization of eftansomatropin alfa in China.
(2) Core clinical assets

Lemzoparlimab (TJC4): A highly differentiated CD47 antibody being developed through a comprehensive clinical development plan for hematologic malignancies and solid tumors in China by I-Mab and globally by AbbVie. I-Mab’s goal is to achieve the first registration of lemzoparlimab in its class in China and facilitate global registration in collaboration with AbbVie, which leads global development and commercialization efforts. To achieve this goal, three clinical programs of lemzoparlimab are ongoing in parallel in both the U.S. and China, which will potentially lead to one or two pivotal clinical trials in 2022.

Lemzoparlimab in combination with rituximab for Non-Hodgkin’s lymphoma (NHL): The clinical trial is ongoing to enroll more patients in the U.S. with additional clinical sites joining in September 2021 in China. The preliminary clinical data is promising in terms of safety and efficacy signals in patients with NHL. The clinical results have been summarized and submitted for presentation at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. The Company expects to, pending approval by the NMPA, initiate a pivotal trial in patients with NHL in 2022 in China.
Lemzoparlimab in combination with AZA in AML and MDS: In May 2021, the first patient was dosed in an abbreviated phase 2 combination clinical trial in patients with newly diagnosed AML or MDS in China. Patient enrollment is on track to be completed in Q4 2021. Based on the preliminary clinical efficacy signal seen in patients on the study, it is expected that this study will potentially lead to a pivotal clinical trial, pending approval by the NMPA, in 2022 in China.
Lemzoparlimab in combination with pembrolizumab in patients with solid tumor: A phase 1b clinical trial is ongoing in the U.S. in patients with selected solid tumors. The preliminary clinical results are expected by the end of 2021 or early 2022. A "basket" clinical trial of lemzoparlimab in combination with a PD-1 antibody in patients with advanced solid tumors is expected to commence in China in Q4 2021.
Lemzoparlimab global phase 1b study, including combination with venetoclax, in patients with AML/MDS is being conducted in the U.S. by AbbVie. The study has the potential to lead to a global pivotal clinical trial where I-Mab will participate for the purpose of simultaneous registration of AML in China.
Uliledlimab (TJD5): A highly differentiated CD73 antibody being developed for solid tumors. Phase 1 clinical trial conducted in the U.S. was completed and the clinical data was presented at ASCO (Free ASCO Whitepaper) 2021 as described below. The Company is advancing the asset in phase 2 clinical trials in both the U.S. and China in selected tumor types in an effort to demonstrate clinical proof-of-concept. In parallel, the Company is exploring a potential global partnering deal.

Differentiated mechanism of action (MoA): the Company presented detailed data at the 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in April that highlighted the unique binding epitopes and structure of uliledlimab that enabled the complete CD73 enzymatic inhibition without the "hook effect," as well as pre-clinical immuno-regulatory and anti-tumor activity as a single agent and in combination with PD-(L)1 antibodies.
Positive phase 1 results in patients with advanced solid tumors: the Company presented detailed U.S. phase 1 clinical data of uliledlimab in combination with atezolizumab in patients with advanced solid tumors at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting. The combination therapy is safe and well-tolerated with no dose-limiting toxicity. All treatment-related adverse events were either grade 1 or grade 2. Uliledlimab demonstrated a linear pharmacokinetic (PK) profile and reached full receptor occupancy on B cells at the middle and high dose levels with no "hook effect." Among the 13 efficacy-evaluable patients dosed at ≥ 10 mg/kg, three patients had complete or partial responses (objective response rate = 23%) and three had stable disease (disease control rate = 46%). The clinical activity was observed in both PD-(L)1 treatment naïve and refractory cancer patients, including one partial response patient who previously failed nivolumab. Tumor types of patients who had complete or partial responses or stable disease included ovarian clear cell carcinoma, non-small cell lung cancer, and a few other cancers. The three responders were identified as the only patients who exhibited higher co-expression of tumor CD73 and PD-L1 as compared to non-responders, indicating a correlation between higher CD73 expression and clinical activity of uliledlimab and a potential role of CD73 as a predictive biomarker to warrant further investigation. The abstract was selected as a "Top 12" research abstract at the conference.
Phase 2 clinical trials: In February 2021, the first patient was dosed in a phase 2 clinical trial of uliledlimab in combination with toripalimab (TUOYI) in patients with advanced solid tumors in China. In parallel, a phase 2 "basket" clinical trial is expected to be initiated in patients with selected advanced solid tumors in the U.S. in Q4 2021.
Plonmarlimab (TJM2): A monoclonal antibody targeting human granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine that plays a critical role in acute and chronic inflammation. The Company recently carried out an interim analysis of its phase 2/3 clinical trial for the treatment of cytokine release syndrome (CRS) in patients with severe COVID-19 in the U.S. The results are reported below.

The interim analysis showed positive preliminary results in patients who were mechanical ventilation free (MVF) at baseline (N=91). Plonmarlimab treatment resulted in a higher MVF rate (83.6% vs. 76.7%) by day 30, a lower mortality rate (4.9% vs. 13.3%) by day 30, higher recovery rates (68.9% vs. 56.7% at day 14 and 80.3% vs. 70.0% at day 30), as well as reduced time to recovery and hospitalization duration, as compared to placebo. The magnitudes of the clinical improvements are comparable to those observed with lenzilumab in a similar patient population.[1] Biomarker results were consistent with the observed clinical outcome and indicated patients treated with plonmarlimab had a reduction in plasma levels of pro-inflammatory cytokines and chemokines critically involved in CRS, including TARC, IP10, GCSF, IL10, IL6, MCP1, IL1RA, TNF-alpha but not interferon-gamma. A transient increase in Neutrophil to Lymphocyte Ratio (NLR) that is commonly associated with disease exacerbation was only observed in placebo. Plonmarlimab was well tolerated in all patients with no significant safety concerns.
The Company is now continuing the Phase 2/3 clinical study in the U.S. and has begun to explore other clinical opportunities associated with CRS in China.
[1] View Source

Efineptakin alfa (TJ107): The world’s first and only long-acting recombinant human interleukin-7 ("rhIL-7"). This asset is clinically positioned as a monotherapy for the treatment of cancer patients with lymphopenia and as a combination immunotherapy with a PD-1 or PD-L1 antibody for cancer treatment. I-Mab has the development, manufacturing, and commercial rights of efineptakin alfa in Greater China from Genexine.

I-Mab is accelerating the clinical development of efineptakin alfa by leveraging accumulative clinical data from multiple previous studies either as a monotherapy or in combination with checkpoint inhibitors in cancer patients, as conducted by I-Mab in China and Genexine and NeoImmuneTech in South Korea and the U.S., respectively.

Efineptakin alfa clinical development in China by I-Mab: (1) A phase 1 clinical trial in China in patients with advanced solid tumors is completed with topline safety and PK/PD data submitted for the 2021 Chinese Society of Clinical Oncology (CSCO) Annual Meeting. (2) A phase 2 clinical trial in patients with GBM: In February 2021, the first patient was dosed, and the study is on track for patient enrollment. (3) Another phase 2 clinical trial of efineptakin alfa in combination with pembrolizumab (Keytruda) in advanced solid tumors was accepted by NMPA and will start when approved in patients with selected solid tumors, including triple-negative breast cancer (TNBC) and head and neck cancers.
Clinical data published by Genexine/NeoImmune Tech: (1) Triple-Negative Breast Cancer (TNBC): Data from the phase 1b/2 Keynote-899 study, presented at SITC (Free SITC Whitepaper) 2020, showed that combination treatment of efineptakin alfa at 1200 ug/kg with pembrolizumab (Keytruda) induced 27.8% ORR in patients with metastatic TNBC. (2) Glioblastoma multiforme (GBM): Interim results from the phase 1 trial (NCT03687957) in newly diagnosed patients with high-grade gliomas that had undergone chemoradiotherapy showed that absolute lymphocyte count (ALC) increased by 1.3 – 4.1 fold at week 4 in a dose-dependent manner and lasted up to 12 weeks after injection, with a one-year survival rate of 83.3% being observed so far.
(3) Other clinical assets

Olamkicept (TJ301): A differentiated IL-6 blocker for ulcerative colitis and other autoimmune diseases. I-Mab entered into a license agreement with Ferring Pharmaceuticals to develop and commercialize olamkicept for Greater China and South Korea in 2016. On April 23, 2021, the Company and Ferring signed a memorandum of understanding (MoU) to explore a possible collaboration to advance the development and commercialization of olamkicept in US and Canada, the European Union and Japan, if so agreed.

Ulcerative colitis: in April 2021, I-Mab reported positive topline phase 2 results for olamkicept in ulcerative colitis. The results demonstrated significantly higher clinical response rates after 12 weeks of treatment in patients receiving 600 mg olamkicept as compared with those on placebo (p=0.032). Significantly more patients in the 600 mg olamkicept group achieved clinical remission and mucosal healing than in the placebo group (p<0.001). The detailed data analysis was presented at the 2021 Digestive Disease Week (DDW) in the U.S. and the 2021 European Crohn’s and Colitis Organisation (ECCO) meeting. A phase 3 clinical trial is being planned.
Enoblituzumab (TJ271): A humanized B7-H3 antibody as an immuno-oncology treatment agent. As an anti-tumor agent, enoblituzumab works through a unique dual mechanism, i.e. ADCC and immune activation. Over the years, MacroGenics has generated sufficient clinical data in cancer patients, which provide a critical guidance for further clinical development of enoblituzumab in the treatment of cancers. In addition, I-Mab’s in-house work is geared towards delineating the combo strategy where enoblituzumab in combination with another treatment agent achieves synergism required for increased clinical efficacy. The Company’s development strategy is to move ahead with a combination therapy with pembrolizumab (Keytruda) in selected cancer types, followed by new combo studies with other validated anti-tumor agent(s). I-Mab licensed the development, manufacturing, and commercialization rights of enoblituzumab in Greater China from MacroGenics.

The Company plans to submit an IND in Q4 2021 to initiate a phase 2 clinical trial of enoblituzumab in combination with pembrolizumab (Keytruda) in patients with selected solid tumors in China. The study is designed as a "basket" clinical trial involving NSCLC and two other selected cancer types based on the previous studies conducted by MacroGenics.
TJ210: A novel monoclonal antibody targeting C5aR1 to treat cancers through myeloid-derived suppressor cells and modulation of tumor micro-environment in favor of enhanced anti-tumor immune response as a novel mechanism of action. The pre-clinical studies have provided ample scientific evidence for the role of TJ210 in the treatment of cancers. Research is continuing, through in vitro and in vivo experimental systems, to identify and validate the most effective combo partner(s) for TJ210 to guide further clinical development of TJ210. I-Mab owns the China rights from MorphoSys and co-develop the asset globally with MorphoSys.

Phase 1 clinical trial in patients with relapsed or refractory advanced solid tumors by I-Mab in the U.S.: In January 2021, the first patient was dosed, and the study is on track.
Phase 1 clinical trial in China: in January 2021, the Company received China NMPA clearance for phase 1 clinical trial of TJ210 in patients with advanced solid tumors. I-Mab expects to commence the study in early 2022.
Pipeline New-Comers as Bi-Specific Antibodies Driven by 2nd Wave Innovation and as "Super Antibodies" by 3rd Wave Innovation Through Transformative Technologies

(1) Bi-Specific Antibodies

The Company’s bispecific antibodies are novel and designed to address the current unmet medical need in oncology where the majority of cancer patients respond poorly to checkpoint inhibitors as their tumors are often characterized as immunologically ‘cold’ tumor type. I-Mab’s bi-specific antibodies are structurally and functionally enabled to convert immunologically resistant ‘cold’ tumors to immunologically responsive ‘hot’ tumors by targeting multiple immune pathways so as to achieve synergistic anti-tumor activities. They can be categorized into three antibody formats, namely PD-L1-based bispecific antibodies, 4-1BB-based conditional T cell engagers, and antibody-cytokine fusion or so-called immuno-cytokines. During the reporting period, two lead bi-specific antibody assets have advanced to Phase 1 clinical trials in the U.S.

TJ-CD4B: A novel Claudin 18.2 and 4-1BB bispecific antibody capable of binding to tumor cells expressing Claudin 18.2, i.e., gastric cancer and pancreatic cancer cells, and stimulating intra-tumoral T cells by the 4-1BB arm designed to become functionally active only upon tumor engagement whilst silent elsewhere.

Pre-clinical studies have demonstrated superior tumor-dependent immune activation with TJ-CD4B compared to 4-1BB monoclonal antibody. The anti-tumor activity is only achieved locally at the tumor site with no hepatotoxicity or systemic side effects that are commonly seen with 4-1BB monoclonal antibodies when used alone. Studies have also demonstrated a memory response that can resist tumor rechallenge for a long-lasting treatment effect.
In June 2021, the first patient was dosed in a phase 1 clinical trial of TJ-CD4B in patients with advanced or metastatic solid tumors in the U.S. To accelerate its clinical development, China sites will join the dose expansion part of the study in Q1 2022, enrolling patients with gastric cancer, gastroesophageal junction carcinoma, esophageal adenocarcinoma, and pancreatic ductal adenocarcinoma.

TJ-L14B: A differentiated PD-L1-based bispecific antibody with the PD-L1 arm as the tumor-dependent T-cell activator and the 4-1BB arm as the conditional T cell activator upon local tumor engagement.

Pre-clinical animal model studies of TJ-L14B have demonstrated a superior anti-tumor effect attributable to the synergism of the two antibody arms in activating intra-tumoral T cells. The 4-1BB arm utilizes the same bispecific antibody format as in TJ-CD4B, aiming to minimize systemic toxicity as a class effect.
In April 2021, the first patient was dosed in a phase 1 clinical trial of TJ-L14B in the U.S. in patients with advanced or metastatic solid tumors. The study is on track.
In addition, other novel bispecific antibodies are currently under pre-clinical development and are expected to advance to the clinical studies in 2022, including:

TJ-C4GM is a fortified CD47 antibody with GM-CSF cytokine. This antibody-cytokine fusion is designed to enhance the anti-tumor effect of CD47 antibody for solid tumors by activating and converting pro-tumor M2 macrophages to anti-tumor M1 macrophages through the GM-CSF arm.
TJ-L1C4 belongs to I-Mab’s PD-L1 based bispecific antibody family and uses CD47 antibody as the other arm.
TJ-L1I7 is an antibody-cytokine fusion protein with the anti-PDL1 antibody fused with IL-7, which is designed to increase both the number and functionality of T cells drawn to the tumor thereby turning "cold" tumor into a more immune-responsive "hot" tumor.
(2) Super Antibodies Enabled by Transformative Technologies

The Company recently launched a discovery initiative (the third wave innovation) to build a new portfolio of next generation of innovative drug candidates characterized as novel "super antibodies". These super antibodies are structurally different from monoclonal or bi-specific antibodies and uniquely enabled by transformative technologies such as an mRNA-based antibody, masked antibody, cell-penetrating antibody and AI-guided cytokine drugs etc. The Company has gained the access to these cutting-edge technology platforms through collaborations as described below. This growing new portfolio of novel drug candidates represents I-Mab’s strong commitment to sustaining the global competitiveness of its pipeline through continued innovation and complements the existing clinical programs.

In collaboration with Complix, an EU-based biotech company, to discover and develop Cell Penetrating Alphabodies (CPAB) for otherwise intractable intracellular drug targets.
In collaboration with Affinity, a Shanghai-based biotech company, to discover and develop masked antibodies for targeted tumor-site activation.
In collaboration with Immorna, an mRNA biotech company, to discover and develop self-replicating mRNA for in vivo synthesized therapeutic biologics.
In collaboration with neoX Biotech, an AI-enabled R&D biotech company, to accelerate the R&D process of novel targets and modalities.
The Company continues to drive innovation and scientific leadership in immuno-oncology globally. These collaborations are expected to be followed by additional partnering deals that are under discussion, which are designed to propel the discovery engine to drive future pipeline growth.

Business Development and Partnering deals

During the reporting period, the Company has completed 7 licensing and partnering deals that are geared to support the next generation of innovative assets. In addition, the Company is in discussion or business negotiation with potential partners on the following opportunities: (1) Eftansomatropin alfa (TJ101) for a commercial partnering deal with a potential partner at a term-sheet stage, for which I-Mab expects to hold MAH and share in significant sales profit; and (2) Other ongoing BD activities, focusing on in-licensing opportunities for the purpose of enriching the Company’s initial commercial portfolio. In addition, the Company is exploring a potential global partnering deal with respect to uliledlimab (TJD5) where I-Mab expects to retain the Greater China rights and grant ex-China rights to a potential global partner.

Transitioning from a Clinical Stage Biotech to Become a Global Biopharma

I-Mab has embarked on a journey to evolve from a clinical stage biotech today to a global biopharma within the next three years. The Company has been expanding its global R&D and corporate footprint and is now globally connected with six sites or offices in China (Shanghai, Beijing, Hangzhou, Guangzhou, Lishui, and Hong Kong) and two sites in the U.S. (Maryland and San Diego). During the reporting period, the Company has made significant progress in advancing its build-up of the manufacturing facility in Hangzhou and its commercialization capability to prepare for the market launch of felzartamab, which has already started in 2021.

Expanding global footprint

(1) A new R&D facility is being established in San Diego, CA, in the U.S. to focus on translational medicine and biomarker research to support the clinical development of I-Mab pipeline assets in the U.S. and China. The center will also host the CMC formulation research and global alliance management. The facility will be operational in Q4 2021; (2) Opening of a new office in Guangzhou, China as a regional hub for clinical development and commercial activities, further aligning the Company’s strategy with the Greater Bay Area ("GBA") initiative. These new sites complement with Company’s existing facilities and are designed to facilitate its ambition to become a global biopharma.

Building manufacturing capability in Hangzhou

To support its growing pipeline and planned production of the upcoming commercial products, the Company has made substantial progress in the construction of a state-of-the-art GMP manufacturing facility in Hangzhou, China. The pilot plant with 3 x 2,000L production lines is on track to become operational by mid-2022. The PD laboratory is already functional to handle I-Mab’s CMC projects. The commercial production facility is being constructed to accommodate up to 8 x 4,000L production lines and is on track to be operational by the end of 2023 or early 2024. The Hangzhou facility has been designed in compliance with Good Manufacturing Practice (GMP) standards adopted by the U.S. Food & Drug Administration (FDA), the China National Medical Products Administration (NMPA), and European Medicines Agency (EMA).

Expanding the commercialization capability for the market launch of felzartamab and other upcoming products

During the reporting period, the Company has advanced to expand the initial commercialization capability in the following four areas. (1) The key commercial strategy for I-Mab is to leverage its key pipeline products, i.e. felzartamab for multiple myeloma and lemzoparlimab for leukemia, e.g. AML and MDS, and lymphoma when combined with rituximab, to become a leader in the hematologic oncology therapeutic area in China. (2) The current expert commercial core team is being expanded to cover all commercialization functions, including regulatory, market research, market access, reimbursement, sales team etc. The team will be ready for scale up as felzartamab approaches the planned market launch. (3) An integrated multi-functional team consisting of different expertise has been assembled and working towards "preparing the organization", "preparing the market" and "preparing the product" for felzartamab. (4) There are ongoing efforts to enrich the initial product portfolio, beyond felzartamab, through in-licensing and commercial partnering opportunities. Potential deals are expected in late 2021 or early 2022.

ESG Update

In July 2021, I-Mab was granted a BBB rating, the highest newly initiated rating among China-based biotech companies, by the MSCI ESG assessment. In August 2021, the Company established an ESG Committee. The committee consists of Ms. Huaqiong Shen, executive director and CEO of I-Mab, and two independent directors, Mr. Chun Kwok Alan Au and Ms. Rong Shao. Mr. Chun Kwok Alan Au also chairs the committee to ensure impartiality. As the oversight body for the Company’s ESG practices, the committee is responsible for supervising the ESG strategies, policies, long-term sustainability objectives and risks of the Company. In addition, the Company also set up an ESG working group to address daily ESG workflows.

I-Mab’s vision has been not only to bring innovative therapies to global patients and create value for its shareholders but is also committed to high corporate governance standards, diversity, green operations, sustainable development, and transparent disclosures. Looking forward, the Company will continuously improve its ESG practice and carry out new initiatives to further integrate ESG factors into its strategies and corporate values and communicate periodic progress with investors in a timely manner.

Corporate Development

I-Mab was added to the MSCI China All Shares Index in May 2021, demonstrating I-Mab’s growing profile and recognition among the global investor communities.
To support its long-term growth, I-Mab’s Board of Directors approved a preliminary proposal for the potential dual listing of the Company’s newly issued shares on the Science and Technology Innovation Board of the Shanghai Stock Exchange (STAR Market). The Company is also considering equity listing on the Main Board of the Hong Kong Stock Exchange under Chapter 18A of the Hong Kong Listing Rules.
I-Mab’s appointment of Ms. Lan Kang as a new member of the Company’s board of directors on August 31, 2021. Ms. Kang is currently a managing director at CBC Group, where she is responsible for managing all the portfolio companies of the Group. Prior to CBC Group, she was an Executive Board Director and SVP of Fosun International and led Fosun’s insurance business globally. She was also on the board of Fosun Pharma and Fosun United Health Insurance. Prior to joining Fosun, Ms. Kang was a Senior Client Partner at Korn/Ferry (KF) International. She successfully developed the Life Sciences practice for KF in mainland China, providing executive search and leadership assessment and human resources consulting to both multinational and local Chinese clients. Prior to that, Ms. Kang was a management consultant at McKinsey & Company, also focusing on the healthcare practice in China. Concurrently, Ms. Mengjiao Jiang, managing director at CBC Group, has resigned from the I-Mab Board due to CBC Group’s internal transition of her roles and responsibilities.
I-Mab held a corporate R&D event in April 2021, focusing on cutting-edge sector insights from industry experts and the latest progress of pipelines from management.
I-Mab expanded the expertise of its board with the appointment of international gastrointestinal oncology expert Dr. Andrew Zhu to its Scientific Advisory Board, and Dr. Ruyi He and Professor Rong Shao to I-Mab’s Board of Directors.
I-Mab was ranked among the top companies by the leading global financial publication Institutional Investor in both the "Honored Companies" and "Best CFO" categories, according to its 2021 All-Asia Executive Team survey.
I-Mab was honored with the T+ Excellent Employer award based on an assessment of best practices in areas such as technological leadership, organization and talent, and commitment to creating a diversified workplace.
I-Mab was ranked as "2021 Top 50 Enterprises of Technology Power" by Frost&Sullivan and LeadLeo.
I-Mab donated RMB 1 million to Henan Charity General Federation for the rescue and reconstruction of flood-hit regions in Henan Province.
First-Half 2021 Financial Results

Cash Position

As of June 30, 2021, the Company had cash, cash equivalents, restricted cash, and short-term investments of RMB 4.8 billion (US $739.2 million), compared with RMB 4.8 billion as of December 31, 2020. Our strong cash balance provides us with adequate funding support and strategic flexibility as we transition from a clinical stage biotech to a global biopharma company over the next few years.

Net Revenues

Total net revenues for the six months ended June 30, 2021 were RMB 17.8 million (US $2.8 million). The total net revenues for the comparable period in 2020 were nil. Revenues generated for the six months ended June 30, 2021 solely consisted of revenues recognized in connection with I-Mab’s strategic collaboration with AbbVie.

Research & Development Expenses

Research and development expenses for the six months ended June 30, 2021 were RMB 593.0 million (US $91.8 million), compared with RMB 442.3 million for the six months ended June 30, 2020. The increase was primarily due to increased CRO service fees to advance the Company’s broad clinical and pre-clinical pipeline, especially for lemzoparlimab (TJC4), uliledlimab (TJD5), and eftansomatropin alfa (TJ101). Share-based compensation expense was RMB 112.7 million (US $17.5 million) for the six months ended June 30, 2021, compared with RMB 132.7 million for the six months ended June 30, 2020.

Administrative Expenses

Administrative expenses for the six months ended June 30, 2021 were RMB 451.5 million (US $69.9 million), compared with RMB 171.4 million for the six months ended June 30, 2020. The increase was primarily due to higher share-based compensation expenses in relation to management, increased professional service expenses (including expenses that were one-off in nature) and expansion in payroll and payroll-related expenses as a result of increased headcount (including new hires in preparation for product launch and commercialization). Share-based compensation expense was RMB 222.0 million (US $34.4 million) for the six months ended June 30, 2021, compared with RMB 97.1 million for the six months ended June 30, 2020. One-time expenses were RMB 69.9 million (US $10.8 million) for the six months ended June 30, 2021, compared with nil for the six months ended June 30, 2020.

Net Loss

Net loss for the six months ended June 30, 2021 was RMB 1,076.5 million (US $166.7 million), compared with RMB 582.9 million for the six months ended June 30, 2020. Net loss per share attributable to ordinary shareholders for the six months ended June 30, 2021 was RMB 6.38 (US $0.99), compared with RMB 4.78 for the six months ended June 30, 2020. Net loss per ADS attributable to ordinary shareholders for the six months ended June 30, 2021 was RMB 14.67 (US $2.28), compared with RMB 10.99 for the six months ended June 30, 2020.

Non-GAAP Net Loss

Non-GAAP adjusted net loss, which excludes share-based compensation expenses, for the six months ended June 30, 2021 was RMB 729.4 million (US $113.0 million), compared with RMB 353.1 million for the six months ended June 30, 2020. Non-GAAP adjusted net loss per share attributable to ordinary shareholders for the six months ended June 30, 2021 was RMB 4.32 (US $0.67), compared with RMB 2.90 for the six months ended June 30, 2020. Non-GAAP adjusted net loss per ADS attributable to ordinary shareholders for the six months ended June 30, 2021 was RMB 9.94 (US $1.54), compared with RMB 6.67 for the six months ended June 30, 2020.

Conference Call and Webcast Information

The Company’s management will host conference calls to discuss the results and updates, and a Mandarin session conference call will be held at 7:00 a.m. ET, and an English session conference call will be held at 8:00 a.m. ET. The conference calls can be accessed by the following Zoom links: