On March 29, 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 full year ended December 31, 2020 and provided key business updates (Press release, I-Mab Biopharma, MAR 29, 2021, View Source [SID1234577263]).

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!

"In an unprecedented year marked by the global pandemic, I-Mab outperformed in delivering outstanding results to accelerate our progress towards becoming a fully-integrated global biopharma company," said Dr. Jingwu Zang, Founder, Chairman and Director of I-Mab. "We have accomplished 18 significant clinical milestones since our IPO last year and our pipeline today has advanced to include three registrational trials with the first NDA planned later this year for a total 19 clinical trials either on-going or to be initiated in both the United States and China."

I-Mab’s globally competitive pipeline has now progressed to include 16 novel or highly differentiated assets with 11 in clinical development stages and five in the pre-clinical stage. The Company’s pre-NDA and core clinical assets of near-term value realization, including felzartamab (TJ202) and eftansomatropin alfa (TJ101), are progressing towards NDA. In addition, two highly differentiated investigational drugs, lemzoparlimab (TJC4) and uliledlimab (TJD5), have achieved critical progress as global front-runners. I-Mab’s next wave of innovative assets, epitomized by the novel bispecific antibodies TJ-L14B and TJ-CD4B, are now moving into clinical trials in the U.S.

In the near-term, I-Mab will continue creating corporate value by delivering on a series of critical milestones including the planned NDA submission for felzartamab in 2021 as well as forging potential strategic global out-licensing partnerships for uliledlimab and other innovative assets and selected in-licensing partnerships to enrich its pipeline. The focused R&D effort is further complemented by the Company’s new discovery initiative to create the next generation of innovative assets through transformative platform technologies.

"We are confident in our innovative R&D strength in immuno-oncology to continue advancing and upgrading our globally competitive pipeline." Dr. Zang concluded.

In addition to creating the near-term value, the Company has also made notable strides in its journey to become a global biopharmaceutical company, which include building a state-of-the-art GMP manufacturing facility in China with a pilot plant and commercial scale production lines.

In parallel, I-Mab has begun to execute a commercialization plan that focuses on building a leading position in hematologic oncology in China, leveraging I-Mab’s core assets (i.e., felzartamab and lemzoparlimab) and additional key product(s) to be in-licensed. As both assets are progressing towards NDA, preparations are being made for product launch and commercialization. Our revenue stream generated from out-licensing deals grew tremendously in 2020 to make I-Mab profitable for the first time and is expected to converge with product sales revenues to be generated in a near term, projecting a promising financial outlook for the Company and its shareholders.

Overview of Operations

I-Mab currently has three registrational trials underway, 16 phase 1 and 2 clinical studies – either ongoing or to be initiated soon in both the U.S. and China – and five on-going pre-clinical programs in 2021. Four additional new discovery programs are set to advance to the pre-clinical development stage by the end of 2021 as a result of the new discovery initiative.

I-Mab has achieved critical advancements in core clinical assets in early 2021. These achievements include the full patient enrollment for felzartamab in the third-line multiple myeloma trial, a key step for the NDA submission that is on track for late 2021, and the initiation to enroll patients for the registrational clinical trial of eftansomatropin alfa. The Company has also set forth with its accelerated clinical development plan for lemzoparlimab, aiming for NDA approval as the first CD47 antibody drug for the treatment of hematologic malignancies (such as MDS, AML and NHL) in China while continuing to advance clinical trials in solid tumors in combination with PD-1 therapy.

These clinical trials are on-going in the U.S. and China with preliminary data readouts planned in Q4 2021 for the non-Hodgkin’s lymphoma (NHL) study and the solid tumor study in the U.S. The Company also plans to initiate a combination clinical trial of lemzoparlimab with felzartamab as a possible novel treatment option for relapsed and refractory and newly diagnosed MM with a potential to become first-line treatment if proven in addition to felzartamab currently being evaluated as a second-line and third-line treatment for MM.

For uliledlimab, a globally competitive and differentiated CD73 antibody, the Company recently completed a phase 1 clinical study in the U.S., which demonstrated favorable safety, PK/PD and receptor occupancy profile, together with observed clinical activity of the investigational drug in cancer patients. The detailed clinical data have been submitted for presentation at ASCO (Free ASCO Whitepaper) 2021. In addition, a combined phase 1/2 clinical trial has been ongoing and the dose expansion part of the trial will be initiated in combination with PD-1 therapy in patients with cancers in China in 2H 2021.

Already operating globally with five hubs in China and the U.S., I-Mab has plans to open a new R&D center in San Diego, CA, focusing on translational medicine and formulation research. In preparation for the market launch of its initial series of products in China, the Company is in construction of a comprehensive biologics manufacturing facility in Hangzhou, China, and is building up its commercialization capabilities.

To support its long-term growth, I-Mab is actively monitoring market conditions and considering potential options for further equity listings on Greater China stock exchanges such as the STAR Market in Shanghai and the Main Board of the Hong Kong Stock Exchange under Chapter 18A of the Hong Kong Listing Rules.

Recent Pipeline Highlights and Upcoming Milestones

Core Clinical Assets – Global Frontrunners

Lemzoparlimab (TJC4): A highly differentiated CD47 antibody being developed for oncology indications. The results of the US phase 1 clinical trial in patients with solid tumor indicate potential clinical advantages of lemzoparlimab in safety and PK with observed clinical activity, which does not require priming dose as compared to other clinical stage CD47 antibodies. Lemzoparlimab is being developed through a comprehensive clinical development plan for hematologic oncology and solid tumor in global collaboration with AbbVie.

Global Collaboration with AbbVie: In September 2020, to facilitate and accelerate the global development and commercialization of lemzoparlimab, I-Mab granted AbbVie a global license valued at US$1.94 billion, including an upfront payment of US$180 million and the first milestone payment of US$20 million based on the phase 1 clinical results. I-Mab retains the rights to develop and commercialize lemzoparlimab in Mainland China, Hong Kong and Macau. We believe that this global collaboration with AbbVie will greatly facilitate the clinical development, manufacturing and commercialization of lemzoparlimab globally and in China.

Hematologic malignancies: Our prioritized development goal is to achieve an accelerated approval of lemzoparlimab in China, ideally as the first CD47 antibody product in China. MDS and possibly NHL are being considered as potential first indication(s) as they hold the high probability of success for accelerated approvals.

(1) With the approved IND, the Company is initiating an abbreviated phase 2 clinical study of lemzoparlimab in combination with AZA in patients with AML and MDS, potentially bridging the clinical study – pending approval by the National Medical Products Administration (NMPA) – to a registrational clinical trial in patients with MDS.

(2) The Company continues to enroll more patients with NHL in a combination clinical trial with rituximab (Rituxan) in the U.S. This clinical trial includes clinical sites in China through an IMCT (international multi-center trial) mechanism in order to potentially bridge – pending approval by the NMPA – to a registrational clinical trial in NHL in China. The preliminary data readout of the NHL trial is set in Q4 2021.

(3) The Company will participate in a global clinical trial to be led by AbbVie in patients with AML for registrational purposes globally by AbbVie and in China by I-Mab.
Solid tumor indications: The Company will continue advancing the current cohort expansion study in the U.S., combining lemzoparlimab with pembrolizumab (Keytruda) to evaluate the safety and efficacy in patients with NSCLC and ovarian cancer. The results of this on-going clinical study are anticipated in Q4 2021. In addition to the on-going US clinical trial, we are in preparation of an IND submission to China’s NMPA to initiate a phase 2 "basket" clinical trial in patients with advanced solid tumors in 2H 2021.

Combination therapy with the existing assets for potential new treatment options: Pre-clinical data generated internally and reported by others support the hypothesis that lemzoparlimab may work additive with other immune pathways, such as the CD38 pathway for multiple myeloma, to offer significantly better treatment efficacy for oncology indications. A clinical trial will be initiated in 2H 2021 in China to evaluate safety and efficacy of combination therapy of lemzoparlimab with felzartamab as a possible novel treatment option for relapsed and refractory and newly diagnosed MM, potentially becoming first-line treatment if proven, in addition to felzartamab currently being evaluated as a second-line and third-line treatment for MM.

Potential upcoming milestones:

The on-going clinical trial with lemzoparlimab in combination with pembrolizumab in patients with NSCLC and ovarian cancers in the U.S. is on track to deliver preliminary results by Q4 2021.

A new clinical trial of lemzoparlimab in combination with PD-1 therapy in patients with selected solid tumors will be initiated in 2H 2021 in China.

An abbreviated phase 2 combination study of lemzoparlimab with AZA in untreated AML and MDS patients is planned to commence in Q2 2021 in China. Patient enrollment is expected to complete by Q4 2021.

Topline results from the on-going NHL clinical study, involving both the U.S. and China clinical sites, are expected by Q4 2021.

The combination study of lemzoparlimab with felzartamab in patients with MM is planned to start in 2H 2021 in China.
Uliledlimab (TJD5): A highly differentiated CD73 antibody for immuno-oncology through modulation of tumor microenvironment. Uliledlimab is shown to strongly suppress tumor growth especially when combined with a PD-(L)1 inhibitor in pre-clinical studies. I-Mab has completed a phase 1 clinical trial in the U.S. with positive results for favorable safety, PK/PD, biomarker analysis and clinical activity of uliledlimab. The topline results have been submitted to ASCO (Free ASCO Whitepaper) 2021.

Differentiated mechanism of action by uliledlimab: The Company will present the mechanistic analysis and pre-clinical data at 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. The key differentiation of uliledlimab when compared to other clinical stage antibodies of the same class is related to its novel epitope, which works through a unique intra-dimer binding mode, resulting in a complete inhibition of the enzymatic activity while avoiding the aberrant pharmacological property known as the "hook effect." With this particular mode of action, uliledlimab has the potential to become a best-in-class CD73 antibody for its clinical advantages.

Phase 1 clinical trial completed in the U.S.: The initial assessment of a phase 1 clinical study investigating uliledlimab monotherapy lead-in followed by combination with atezolizumab (Tecentriq), in patients with solid tumors has been completed. Topline results from the study demonstrate that uliledlimab is safe and well tolerated at the dose range evaluated. The study also demonstrated favorable clinical activity of uliledlimab in patients with advanced solid tumors. I-Mab has submitted an abstract to present the topline results at 2021 ASCO (Free ASCO Whitepaper) annual meeting to be held in June.

Continued clinical development: The Company is looking to expand the on-going clinical study of uliledlimab with a PD-1 antibody toripalimab (TUOYI) in patients with advanced or metastatic cancers in China to further evaluate clinical efficacy of uliledlimab in a phase 2 combination clinical trial with toripalimab in selected solid tumors by a "basket" trial design in 2H 2021.

Potential upcoming milestones:

I-Mab has submitted an abstract to present the phase 1 topline results at the June 2021 ASCO (Free ASCO Whitepaper) annual meeting.

The expansion study in patients with NSCLC and other selected tumors has been initiated in over 15 sites across China. The results are expected in 2022.
Core Clinical Assets – Pre-NDA Products

Felzartamab (TJ202): A potential highly differentiated CD38 antibody for multiple myeloma (MM) and systemic lupus erythematosus (SLE). Felzartamab is a pre-NDA product in I-Mab’s pipeline being positioned to launch in the near-term in China to cover third-line and second-line MM treatment. Its potential role as a first-line MM treatment in combination with lemzoparlimab is being explored.

Multiple myeloma: Two registrational studies of felzartamab are on-going. The third-line registrational trial has completed patient enrollment. The Company is on track to submit an NDA in 2H 2021. The second-line combination therapy with lenalidomide is on track and is continuing to enroll patients. Full patient enrollment (N=291) for that trial is expected in Q3 2021. In addition, a new IND for combination trial of felzartamab with lemzoparlimab for MM will be submitted in Q2 2021 and the study will be initiated in 2H 2021 in China. This combination therapy, a possible first-line treatment if proven, has the potential to be a novel treatment option for relapsed and refractory and newly diagnosed MM.
SLE: The Company is awaiting IND approval by the NMPA and a phase 1b trial in patients with SLE will be initiated 2H 2021 in China.
Potential upcoming milestones:

I-Mab expects to submit an NDA for felzartamab as a third-line treatment for MM to the NMPA in Q4 2021.

Completion of patient enrollment of the second-line registrational study for MM is anticipated in Q3 2021.

In China, a new IND for combination trial of felzartamab with lemzoparlimab as a possible novel treatment option for relapsed and refractory and newly diagnosed MM with the potential to become first-line treatment if proven will be submitted in Q2 2021 and the study will be initiated in 2H 2021.

Initiation of phase 1b SLE trial is on track for 2H 2021.
Eftansomatropin alfa (TJ101): A differentiated long-acting growth hormone for pediatric growth hormone deficiency (PGHD). Eftansomatropin has a product advantage as it is the only rhGH in its proprietary fusion protein format. Its safety and efficacy have been demonstrated in a phase 2 clinical trial in EU.

In February 2021, I-Mab achieved the first patient dosing of a phase 3 registrational clinical trial (NCT04633057) in China to assess the clinical efficacy, safety of eftansomatropin alfa in PGHD patients as a weekly treatment. This registrational phase 3 trial ("TALLER") will enroll 165 patients across multiple centers in China, with the primary objective of demonstrating non-inferiority of 1.2 mg/kg/week of eftansomatropin alfa administered SC, compared to Norditropin, a daily rhGH marketed in China.
Potential upcoming milestones:

The primary clinical data are expected to be available in Q2 2023 to support the planned NDA submission in China.
Efineptakin alfa (TJ107): The world’s first long-acting recombinant human interleukin-7. This asset is positioned clinically as a monotherapy for the treatment of cancer patients with lymphopenia and as a combination immunotherapy to pair with PD-1 or PD-L1 antibody for cancer treatment:

The on-going phase 1b clinical trial in China is investigating the safety, tolerability and PK/PD profile of efineptakin alfa in patients with advanced solid tumors. The results of the study are expected in Q2 2021.
The current clinical development plan is to evaluate the therapeutic role of efineptakin alfa (1) as a monotherapy for cancer patients with lymphopenia and (2) as a combination therapy with PD-1/PD-L1 antibody for cancers. The outcome of the studies will facilitate the development path of efineptakin alfa towards pivotal clinical trials in China.

Cancers with lymphopenia. In December 2020, I-Mab initiated a phase 2 randomized, single-blind, placebo-controlled clinical trial (NCT04600817) to evaluate the safety and efficacy of efineptakin alfa in glioblastoma multiforme (GBM) patients with lymphopenia. The primary outcome of the study is the percentage of patients with an increase in the absolute lymphocyte counts and associated clinical response in relation to the treatment with efineptakin alfa.
Combination therapy with PD-1/PD-L1 agents. Our partner Genexine recently released encouraging new data of a phase 1b/2 study of efineptakin alfa in combination with pembrolizumab (KEYTRUDA) for the treatment of relapsed or refractory triple-negative breast cancer (TNBC) in terms of safety and efficacy signals. I-Mab plans to submit an IND in China in 2H 2021 to initiate a phase 2 clinical trial following a basket trial design, in which efineptakin alfa is combined with a PD-1 antibody for the treatment of selected tumor types, including TNBC.
Other Clinical Assets

Plonmarlimab (TJM2): A granulocyte-macrophage colony stimulating factor (GM-CSF) monoclonal antibody for the treatment of rheumatoid arthritis and CRS-related therapies:

Cytokine release syndrome associated with severe COVID-19: I-Mab is conducting a phase 2 clinical trial with plonmarlimab for the treatment of cytokine release syndrome associated with severe and critically ill COVID-19 patients (NCT04341116) to potentially save lives of patients with severe COVID-19. The clinical trial has progressed to the second part, aiming to evaluate the efficacy, safety and cytokine levels following a single dose of plonmarlimab at 6 mg/kg or placebo (best supportive care) in patients with severe COVID-19. An interim analysis is planned in Q2 2021.
Rheumatoid arthritis: I-Mab has initiated a phase 1b clinical study with plonmarlimab in patients with rheumatoid arthritis (RA). This trial is a multi-center, double-blind, placebo-controlled study involving about 63 patients who will receive a single dose or multiple doses of the treatment for up to eight weeks. The single dose escalation part is aimed to complete by 2H 2021.
Olamkicept (TJ301): A potential highly differentiated IL-6 blocker for ulcerative colitis:

I-Mab has successfully completed a phase 2 study in 91 patients with active ulcerative colitis (UC) in Greater China and South Korea (NCT03235752) and is at the final stages of data analysis.
I-Mab will continue to advance the development and maximize the potential value of this differentiated drug molecule through our global partnership with Ferring.
Enoblituzumab: A potential highly differentiated humanized B7-H3 antibody as an immuno-oncology treatment. I-Mab has the development and commercial rights of enoblituzumab in Greater China from MacroGenics.

I-Mab plans to submit a pre-IND in Q2 2021 to initiate a phase 2 clinical trial of enoblituzumab in combination with a PD-1 antibody in patients with certain 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.
I-Mab has plans to evaluate the therapeutic role of enoblituzumab in combination with other targeted cancer therapies as a potential front-line treatment for selected cancers. The pre-clinical work is in progress. Submission of an IND is anticipated by the end of 2021 to start the clinical study.
TJ210: A novel monoclonal antibody targeting myeloid derived suppressor cells as a cancer immunotherapy through a novel mechanism of action. This asset is in clinical development through partnership with MorphoSys.

Pre-clinical development update: TJ210 is a novel human antibody directed against C5aR1 derived from MorphoSys’ HuCAL Platinum technology. The findings of pre-clinical studies in relation to characterization of unique antibody epitope, pharmacological profile and anti-tumor properties of TJ210 were presented at the 2020 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting.

Current clinical development plan: A phase 1 clinical trial is now enrolling patients in the U.S. to evaluate the safety, tolerability and PK/PD profiles of TJ210 in cancer patients. The program is expected to further evolve into a combination clinical trial with a PD-1 antibody in selected cancer types. In addition, with the IND approved by China’s NMPA in February 2021, I-Mab expects to commence a phase 1b clinical trial in 2H 2021. The results of the clinical studies in the U.S. and China, in relation to safety, PK/PD profiles, biomarker analysis and early efficacy signals, as described above will facilitate the further clinical development of TJ210.
Two new bi-specific antibodies have entered the clinical development stage in 2021

TJ-CD4B: A novel bi-specific antibody with the Claudin 18.2 arm as a specific tumor-engager and the 4-1BB arm as a conditional T cell activator upon tumor engagement.

TJ-CD4B is a novel and tumor-dependent bi-specific antibody for the treatment of gastric and other cancers which is being developed under collaboration with ABL Bio. Our pre-clinical studies have demonstrated that TJ-CD4B is 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 be activated only upon tumor engagement whilst silent elsewhere. Thus, TJ-CD4B effectively maintains a strong tumor binding property and anti-tumor activity attributable to a synergistic effect of both Claudin 18.2 antibody and 4-1BB antibody while it avoids or minimizes liver toxicity and systemic immunotoxicity commonly seen with 4-1BB antibodies as a drug class. I-Mab received the IND approval by the U.S. FDA on March 27, 2021 and aims to commence a phase 1 clinical trial in Q2 2021 in patients with advanced solid tumors including gastric cancer to assess the safety, tolerability, PK/PD and preliminary treatment efficacy. In addition, I-Mab will submit a separate IND with the China NMPA in 2H 2021 by leveraging the clinical data generated from the U.S. study to commence parallel clinical development in China.
TJ-L14B: A differentiated bi-specific antibody with the PD-L1 arm as a tumor-site T cell activator and the 4-1BB arm as a conditional T cell activator upon tumor engagement.

Being developed jointly with ABL Bio, TJ-L14B is a differentiated PD-L1-based bi-specific 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 tumor engagement. Pre-clinical tumor animal model studies of TJ-L14B have demonstrated a superior anti-tumor effect attributable to mechanistic synergism of the two antibody arms in activating intra-tumoral T cells. The 4-1BB arm utilizes the same bi-specific antibody format aimed to minimize systemic toxicity as a class effect. With the approved IND from the U.S. FDA, a phase 1 dose escalation clinical study is about to be initiated to assess the safety, tolerability, PK/PD and preliminary efficacy in patients with advanced (unresectable) or metastatic solid tumors.
Pre-Clinical Assets

A number of novel molecules are currently under pre-clinical development, such as: (1) TJX7, a novel monoclonal antibody directed against CXCL13 for the treatment of autoimmune diseases. I-Mab has recently concluded a pre-IND meeting with the U.S. FDA. (2) TJ-C4GM is a fortified CD47 antibody with GM-CSF attached. 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. The results of the pre-clinical studies support the novel mechanism of action. (3) TJ-L1I7 is another 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 to more immune-responsive "hot" tumor. (4) TJ-L1C4 belongs to I-Mab’s PD-L1 based bi-specific antibody family and uses CD47 antibody as the other arm. The candidate molecule is being developed at an early pre-clinical stage.
Commercialization Capability

In August 2020, I-Mab appointed Mr. Ivan Yifei Zhu as Chief Commercial Officer, a high-caliber commercial leader in China, to prepare for the market launch of its initial series of products in China.
Our commercialization strategy is designed to build a leading hematologic oncology franchise in China through I-Mab’s unique product portfolio that includes felzartamab (TJ202) for multiple myeloma, lemzoparlimab (TJC4) for various leukemia indications and a late-stage asset/product to be in-licensed to cover lymphoma indications. This unique portfolio of the three key products enables I-Mab to have a near-complete coverage of major disease indications within the hematologic therapeutic area in China and offers an advantageous position to explore a near-cure therapeutic goal for certain hematologic oncology indications through additional drug combinations.
Towards building a leading hematologic oncology franchise in China, I-Mab is laying foundations and progressing efficiently towards becoming an integrated commercial organization, encompassing market access, medical marketing, supply chain and sales teams. The initial effort of the sales organization is to focus on the launch readiness of felzartamab, the Company’s first hematologic oncology product, by targeting top academic centers and hospital networks across China where the target patient population accounting for majority of national cases is concentrated.
Manufacturing Facility

I-Mab has made significant progress in building a comprehensive biologics manufacturing facility in Hangzhou, China (the "Hangzhou Facility").
The Hangzhou Facility aims to have a pilot plant capacity of 2 production lines (1 line configured with 2 x 2,000L and another line with 1 x 2,000L) by 2022 and commercially progressive capacity up to 8 x 4,000L to become operational by the end of 2023.
The Hangzhou Facility, when operational, will exclusively serve I-Mab’s increasing CMC and manufacturing needs for all on-going and future clinical trials in the U.S. and China and the sustained production of its planned commercial products. The Hangzhou Facility will enable the Company to control the quality and manufacturing schedules tailored to its development and commercialization needs. Importantly, it will significantly reduce our production cost burden and cost of goods as a whole.
Corporate Achievements

In March 2021, I-Mab reported substantial net revenues of RMB 1,542.7 million (US $236.4 million) and net income on a GAAP basis of RMB 470.9 million (US $72.2 million) for the full year of 2020, achieving corporate profitability for the first time in the Company’s history.
In March 2021, I-Mab secured collaborations with Complix, an EU-based biotech company, and Affinity, a Shanghai-based biotech company, gaining access to cutting edge technology platforms to develop its next generation of novel and highly differentiated drug candidates.
In December 2020, I-Mab’s American Depositary Shares (ADS) were selected for inclusion in the NASDAQ Biotechnology Index (Nasdaq: .NBI), based on a set of eligibility criteria including minimum market capitalization and average daily trading volume.
In December 2020, I-Mab appointed leading Immunology and Hematology experts Dr. Chen Dong and Dr. Jun Ma to its Scientific Advisory Board.
In November 2020, I-Mab received BioCentury-Bay Helix’s "Deal of the Year" award for the global strategic collaboration with AbbVie to develop and commercialize lemzoparlimab. I-Mab was also named "10 Biotechs to Know in China" by FiercePharma and listed as "50 Smartest Companies in China" by MIT Technology Review.
In September 2020, I-Mab raised approximately US$418 million through a private placement by a consortium of institutional investors led by Hillhouse Capital.
In September 2020, I-Mab and AbbVie entered into a strategic global collaboration to develop and commercialize lemzoparlimab (TJC4). The total upfront plus milestone payments as well as the potential value of the right of first negotiation in relation to the two additional CD47-based bi-specific antibodies amounted to US $2.94 billion, making this deal the largest cross-border out-licensing transaction from China by total value.
In May 2020, I-Mab opened its Hong Kong office as a regional hub for capital markets and investor relations activities, further benefiting from the Greater Bay Area economic development initiative in the region.
Full Year 2020 Financial Results

Cash Position

As of December 31, 2020, the Company had cash, cash equivalents, restricted cash and short-term investments of RMB 4.8 billion (US $734.1 million), compared with RMB 1.2 billion as of December 31, 2019. The current cash on hand is sufficient to fund operations through 2023, including data readouts on core clinical assets such as lemzoparlimab and uliledlimab and commercialization in China of pre-NDA assets felzartamab and efineptakin alfa.

Net Revenues

Total net revenues for the full year of 2020 were RMB 1,542.7 million (US $236.4 million), compared with RMB 30.0 million for the full year of 2019. The revenues generated for the full year of 2020 solely consisted of the revenues recognized in connection with the strategic collaboration with AbbVie.

Research & Development Expenses

Research and development expenses for the full year of 2020 were RMB 984.7 million (US $150.9 million), compared with RMB 840.4 million for the full year of 2019. The increase was primarily due to the increase in employee benefit expenses, which consist of share-based compensation and payroll expenses, to support expansion of research and development programs.

Administrative Expenses

Administrative expenses for the full year of 2020 were RMB 402.4 million (US $61.7 million), compared with RMB 654.6 million for the full year of 2019. The decrease was primarily due to reduced share-based compensation expenses of RMB 305.7 million (US $46.9 million).

Other Income (Expenses), net

Net other income for the full year of 2020 was RMB 412.9 million (US $63.3 million), compared with net other expenses of RMB 20.2 million for the full year of 2019. The change was primarily attributable to the RMB 407.6 million gain recognized as a result of the transfer of equity of I-Mab Hangzhou from I-Mab Hong Kong to a group of domestic investors in China. The equity transfer realized the fair value appreciation in the pipeline assets as well as the employment of a team of designated management and workforce.

Net Income

Net income for the full year of 2020 was RMB 470.9 million (US $72.2 million), compared with a loss of RMB 1,452.0 million for the full year of 2019. Net income per share attributable to ordinary shareholders for the full year of 2020 was RMB 3.51 (US $0.54), compared with net loss per share attributable to ordinary shareholders of RMB 201.19 for the full year of 2019. Net income per ADS attributable to ordinary shareholders for the full year of 2020 was RMB 8.07 (US $1.24), compared with net loss per ADS attributable to ordinary shareholders of RMB 462.74 for the full year of 2019.

Non-GAAP Net Income

Non-GAAP adjusted net income, which excludes share-based compensation expenses, for the full year of 2020 was RMB 997.1 million (US $152.8 million), compared with non-GAAP adjusted net loss of RMB 936.7 million for the full year of 2019. Non-GAAP adjusted net income per share attributable to ordinary shareholders for 2020 was RMB 7.43 (US $1.14), compared with non-GAAP adjusted net loss per share attributable to ordinary shareholders of RMB 131.39 for the full year of 2019. Non-GAAP adjusted net income per ADS attributable to ordinary shareholders for the full year of 2020 was RMB 17.09 (US $2.62), compared with non-GAAP adjusted net loss per ADS attributable to ordinary shareholders of RMB 302.20 for the full year of 2019.

Conference Call and Webcast Information

The Company will host a live conference call and webcast on March 29, 2020 at 8:00 a.m. ET. Participants must register in advance of the conference call. Details are as follows:

Registration Link: View Source

Conference ID: 4848159
Upon registering, each participant will receive a dial-in number, Direct Event passcode, and a unique access PIN, which can be used to join the conference call.

A webcast replay will be archived on the Company’s website for one year after the conclusion of the call at View Source

A telephone replay will be available approximately two hours after the conclusion of the call. To access the replay, please call +1-855-452-5696 (U.S.), +61-2-8199-0299 (International), 400-632-2162 (Mainland China), or 800-963-117 (Hong Kong). The conference ID number for the replay is 4848159.

On March 29, 2021 Celldex Therapeutics, Inc. (NASDAQ:CLDX) reported business and financial highlights for the fourth quarter and year ended December 31, 2020 (Press release, Celldex Therapeutics, MAR 29, 2021, View Source [SID1234577262]).

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!

"Celldex made significant progress across our pipeline in 2020 and today continued this momentum with the announcement of compelling interim results from our ongoing Phase 1b study of CDX-0159 in chronic inducible urticaria where we have observed an 80% complete response rate and a well-tolerated safety profile to date," said Anthony Marucci, Co-founder, President and Chief Executive Officer of Celldex Therapeutics. "These data support the novel mechanism of CDX-0159 and the potential broad applicability of this compound in mast cell driven diseases. Based on these results, we are expanding the study to also include patients with cholinergic urticaria and look forward to presenting updated results from the cold induced and symptomatic dermographism cohorts this summer. We also anticipate results from the ongoing Phase 1b study in chronic spontaneous urticaria by the end of the year and are on track to initiate a third study in prurigo nodularis in the fourth quarter."

"In 2020, we also continued to advance our oncology programs, presenting data from our CDX-1140 program supporting this candidate as a best in class CD40 agonist and initiating a Phase 1 study of CDX-527, the first candidate from our bispecific platform, into the clinic. We anticipate data updates from both of these programs later this year and look forward to what promises to be a busy and exciting time for the Company."

Recent Pipeline Highlights

While Celldex’s clinical development programs have not been significantly, negatively impacted by COVID-19 to date, the Company continues to carefully monitor the evolving situation closely across all development programs and work to minimize potential impact/disruptions.

CDX-0159—a humanized monoclonal antibody developed by Celldex that binds the KIT receptor with high specificity and potently inhibits its activity. The KIT receptor tyrosine kinase is expressed in a variety of cells, including mast cells, which mediate inflammatory responses such as hypersensitivity and allergic reactions. KIT signaling controls the differentiation, tissue recruitment, survival and activity of mast cells. Results from a Phase 1a dose escalation study of CDX-0159 were featured in a late breaking presentation in June at the EAACI Annual Congress 2020. CDX-0159 demonstrated a favorable safety profile as well as profound and durable reductions of plasma tryptase, indicative of systemic mast cell ablation.

Celldex initiated a Phase 1b open label study designed to evaluate the safety of a single dose (3.0 mg/kg) of CDX-0159 administered intravenously in December of 2020. Up to 20 patients with cold contact urticaria (ColdU; n=10) or symptomatic dermographism (SD; n=10) who are refractory to antihistamines are being enrolled. Patients’ symptoms are induced via provocation testing that resembles real life triggering situations. Secondary and exploratory objectives include pharmacokinetic and pharmacodynamic assessments, including changes from baseline provocation thresholds, measurement of tryptase and stem cell factor levels, clinical activity outcomes (impact on urticaria symptoms, disease control, clinical response), quality of life assessments and measurement of tissue mast cells through skin biopsies. The study is being conducted by Dr. Marcus Maurer, Professor of Dermatology and Allergy at Charité – Universitätsmedizin in Berlin.

Interim data from this study were reported earlier today. Fifteen out of 20 planned patients with antihistamine refractory CIndU had received a single intravenous infusion of CDX-0159 at 3 mg/kg, including nine patients with ColdU and six patients with SD. Safety results were reported for all 15 patients; activity results were reported for all patients assessed for at least 15 days/2 weeks after treatment (n=10; 7 ColdU and 3 SD). Patients had high disease activity as assessed by provocation threshold testing. In ColdU and SD pts, baseline critical temperature thresholds were 18.7 +/- 2.7 °C (range: 5-27°C) and FricTest thresholds were 3.7 +/- 0.3 (range: 3-4) of 4.

Eight of 10 patients (7 ColdU; 1 SD) experienced a complete response (CR) as assessed by provocation threshold testing. The remaining two patients (both with SD), had been recently treated and were followed for two weeks. One patient experienced a partial response (PR) thus far and one patient reported symptomatic improvement (decreased itching). All patients will continue to be assessed for response through week 12.
Patient global assessment (Pat-GA) and physician global assessment (Phy-GA) results were consistent with provocation testing results.
Measurements of serum tryptase levels are available for only the first six patients evaluated for activity, all with ColdU. The mean baseline was 3.3 +/- 0.2 ng/ml and levels on day 15 after treatment were at or below the limit of detection. These patients all experienced complete responses.
CDX-0159 was generally well tolerated. Six of 15 patients had mild infusion reactions, generally areas of localized redness and itching, which resolved rapidly. A single severe infusion reaction was observed (brief loss of consciousness, followed by shaking and sweating). The patient was treated with antihistamines and steroids; no epinephrine was administered. The patient rapidly recovered and was hospitalized for observation with no further manifestations of this event. Importantly, there was no evidence of mast cell activation as measured by decreases in serum tryptase levels shortly after the infusion and further at a later time point.
Through day 15, three patients had transient, mild decreases in hemoglobin, and no patients had meaningful declines in white blood cells.
Enrollment is currently being completed in the ColdU and SD cohorts. Based on these compelling results, the study is being expanded to also include 10 patients with cholinergic urticaria and enrollment of these patients is planned to begin in May of 2021.
Updated results from additional patients with cold induced urticaria and symptomatic dermographism and long term follow up that continues to characterize magnitude and duration of treatment effect and their link to changes in tryptase levels are expected this summer.

Celldex initiated dosing in a Phase 1b multi-center study of CDX-0159 in chronic spontaneous urticaria (CSU) in October. This study is a randomized, double-blind, placebo-controlled clinical trial designed to assess the safety of multiple ascending doses of CDX-0159 in up to 40 patients with CSU who remain symptomatic despite treatment with antihistamines. Secondary and exploratory objectives include pharmacokinetic and pharmacodynamic assessments, including measurement of tryptase and stem cell factor levels and clinical activity outcomes (impact on urticaria symptoms, disease control, clinical response) as well as quality of life assessments. Results from the study are expected by the end of 2021.

In February 2021, Celldex announced that development of CDX-0159 will be expanded into prurigo nodularis (PN), a chronic skin disease characterized by the development of hard, intensely itchy (pruritic) nodules on the skin. Mast cells through their interactions with sensory neurons and other immune cells are believed to play an important role in amplifying chronic itch and neuroinflammation. Initiation of this study is planned for the fourth quarter of 2021. Celldex is also exploring additional mast cell driven diseases for potential future development, including mast cell activation syndromes, asthma, allergic conditions and mast cell driven gastrointestinal disorders.

Manufacturing activities are also progressing as planned to support the introduction of the CDX-0159 subcutaneous formulation into the clinical program in the third quarter of 2021.
CDX-1140—a potent CD40 human agonist antibody developed by Celldex that the Company believes has the potential to successfully balance systemic doses for good tissue and tumor penetration with an acceptable safety profile.

In the Phase 1 dose-escalation study of CDX-1140 in patients with recurrent, locally advanced or metastatic solid tumors and B cell lymphomas, both the monotherapy and combination with CDX-301 dose escalation portions of the trial are complete with an identified maximum tolerated dose (MTD) and recommended dose of CDX-1140 at 1.5 mg/kg—one of the highest systemic dose levels in the CD40 agonist class. Expansion cohorts are actively recruiting including:

CDX-1140 with KEYTRUDA (pembrolizumab) in patients who have progressed on checkpoint therapy; and,
A combination of CDX-1140 with standard of care chemotherapy in first line metastatic pancreatic cancer.
Updated data from this program are expected to be presented later this year.

Updated interim data from the ongoing Phase 1 study were presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 35th Anniversary Annual Meeting & Pre-Conference Programs (SITC 2020) in November 2020. Analysis was focused on patients treated at the MTD and recommended dose of 1.5 mg/kg. 41 patients had been treated at the 1.5 mg/kg dose at the time of data cutoff (n=25 monotherapy; n=16 in combination with CDX-301, a dendritic cell growth factor used as a priming agent to increase the number of dendritic cells in blood and tissue available for CDX-1140 activation). 29 patients had post-treatment scans performed and five patients had not reached their first post-treatment response assessment. In addition, preliminary safety data from the combination cohort with pembrolizumab (n=9; 4 at 0.72 mg/kg and 5 at 1.5 mg/kg CDX-1140) were also presented. CDX-1140 monotherapy and in combination with CDX-301 or pembrolizumab was generally well tolerated with mostly grade 1 or grade 2 drug related adverse events. Activity at 1.5mg/kg dose of CDX-1140 to date included:

An ongoing (6+ months) complete response (CR) in a patient with follicular lymphoma treated with CDX-1140 in combination with CDX-301; notable tumor shrinkage and/or necrosis in 6 patients with squamous cell head and neck cancer (SCCHN), including extensive tumor cavitation/necrosis of a large baseline protruding neck mass associated with decreased tumor pain in a patient; and stable disease (n=10) for 11 to 32 weeks.
CDX-1140 at 1.5 mg/kg provided good systemic exposure that enhanced the distribution into tissues and tumor and resulted in marked changes in the tumor microenvironment (TME) consistent with a more inflammatory and less immunosuppressive state as demonstrated by gene expression analysis. Interferon signaling and cytotoxicity pathways were most highly upregulated, while immunosuppression via TGFb signaling and metastatic pathways were downregulated, marking the first clear demonstration in patients of biological activity within the TME for a systemically administered agonist anti-CD40 mAb.
CDX-527—the first candidate developed by Celldex from its bispecific platform which utilizes the Company’s proprietary highly active anti-PD-L1 and CD27 human antibodies to couple CD27 co-stimulation with blockade of the PD-L1/PD-1 pathway.

In August 2020, Celldex initiated a Phase 1 dose-escalation study in up to ~90 patients with advanced or metastatic solid tumors that have progressed during or after standard of care therapy to be followed by tumor-specific expansion cohorts. The study is designed to determine the MTD during a dose-escalation phase and to recommend a dose level for further study in the subsequent expansion phase. The expansion is designed to further evaluate the tolerability, and biologic and anti-tumor effects of selected dose level(s) of CDX-527 in specific tumor types. Initial data from the Phase 1 study are expected to be presented later this year.
Fourth Quarter and Twelve Months 2020 Financial Highlights and 2021 Guidance

Cash Position: Cash, cash equivalents and marketable securities as of December 31, 2020 were $194.4 million compared to $199.6 million as of September 30, 2020. The decrease was primarily driven by fourth quarter cash used in operating activities of $5.2 million. At December 31, 2020, Celldex had 39.6 million shares outstanding.

Revenues: Total revenue was $3.8 million in the fourth quarter of 2020 and $7.4 million for the year ended December 31, 2020, compared to $0.9 million and $3.6 million for the comparable periods in 2019. The increase in revenue was primarily due to the $1.8 million milestone payment from Rockefeller University related to our manufacturing and development services agreement and an increase in services performed under our manufacturing and research and development agreements with Rockefeller University and Gilead Sciences, partially offset by a decrease in services performed under our manufacturing and research and development agreement with Duke University.

R&D Expenses: Research and development (R&D) expenses were $10.4 million in the fourth quarter of 2020 and $42.5 million for the year ended December 31, 2020, compared to $10.3 million and $42.7 million for the comparable periods in 2019. The decrease in R&D expenses was primarily due to a decrease in contract research and facility expenses, partially offset by an increase in clinical trials and contract manufacturing expenses.

G&A Expenses: General and administrative (G&A) expenses were $3.6 million in the fourth quarter of 2020 and $14.5 million for the year ended December 31, 2020, compared to $3.2 million and $15.4 million for the comparable periods in 2019. The decrease in G&A expenses was primarily due to a decrease in stock-based compensation and facility expenses.

Intangible Asset Impairment: The Company recorded a non-cash partial impairment charge of $14.5 million related to the TAM program IPR&D asset in the fourth quarter of 2020 as a result of changes in the projected development and regulatory timelines for the program. The Company recorded a non-cash impairment charge of $3.5 million related to the CDX-3379 IPR&D asset in the second quarter of 2020 as a result of the discontinuation of the CDX-3379 program.

Changes in Fair Value Remeasurement of Contingent Consideration: During the year ended December 31, 2020, the Company recorded a $4.2 million gain on the fair value remeasurement of contingent consideration primarily due to updated assumptions for CDX-3379 related milestones due to the discontinuation of the CDX-3379 program partially offset by changes in discount rates and the passage of time.

Net Loss: Net loss was $21.9 million, or ($0.55) per share, for the fourth quarter of 2020 and $59.8 million, or ($2.02) per share, for the year ended December 31, 2020, compared to a net loss of $10.4 million, or ($0.64) per share, for the fourth quarter of 2019 and $50.9 million, or ($3.51) per share, for the year ended December 31, 2019.

Financial Guidance: Celldex believes that the cash, cash equivalents and marketable securities at December 31, 2020 are sufficient to meet estimated working capital requirements and fund planned operations through 2023.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ USA.

On March 29, 2021 Cellectis S.A. (NASDAQ: CLLS – EURONEXT GROWTH: ALCLS) (the "Company"), a clinical-stage biotechnological company employing its core proprietary technologies to develop best-in-class products based on gene-edited allogeneic CAR T-cells in the field of immuno-oncology, reported that it has filed a prospectus supplement with the Securities and Exchange Commission ("SEC") relating to an At-The-Market (ATM) program, pursuant to which it may offer and sell to eligible investors a total gross amount of up to $125.0 million of American Depositary Shares ("ADS"), each ADS representing one ordinary share of Cellectis, from time to time in sales deemed to be an "at the market offering" pursuant to the terms of a sales agreement with Jefferies LLC ("Jefferies"), acting as sales agent (Press release, Cellectis, MAR 29, 2021, View Source [SID1234577261]). The timing of any sales will depend on a variety of factors. The ATM program is presently intended to be effective through the expiration of the existing registration statement, i.e. until June 2, 2023, unless terminated prior to such date in accordance with the sales agreement or the maximum amount of the program has been reached.

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 Company currently intends to use the net proceeds, if any, of sales of ADSs issued under the program (i) to fund the research and development of its product candidates, (ii) to pursue new human therapeutics approaches based on its proprietary gene editing technology outside of oncology, (iii) to fund manufacturing activity in its proprietary state-of-the-art facility in Raleigh, North Carolina, and (iv) for working capital and general corporate purposes.

Jefferies, as sales agent, will use commercially reasonable efforts to arrange on the Company’s behalf for the sale of all ADSs requested to be sold by the Company, consistent with Jefferies’ normal sales and trading practices. Sales prices may vary based on market prices and other factors. Only eligible investors (as described in greater detail below) may purchase ADSs under the ATM program.

The ADSs and the underlying ordinary shares will be issued through a capital increase without shareholders’ preferential subscription rights under the provisions of Article L. 225-138 of the French Commercial Code (Code de commerce) and pursuant to the 13th and/or 15th resolutions adopted by the Annual General Meeting of Shareholders held on June 29, 2020 (or any substitute resolutions, adopted from time to time), within the limit of a maximum number of 12,799,700 ordinary shares (being the maximum authorized by the shareholders for each such resolution), representing a maximum potential dilution of approximately 29.74% based on the existing share capital of the Company.

The ATM program may only be issued to the categories of investors defined in the 13th and/or 15th resolutions (or any similar resolutions that may be substituted to them in the future), comprising (i) any person or legal entity, whether French or foreign (i.e., non-French), that invests on a regular basis or has invested at least €5 million over the preceding 36 months in the health or biotechnology sector and/or (ii) any industrial company, institution or entity, whether French or foreign (i.e., non-French), active in the health or biotechnology sectors or any affiliate thereof. The new ordinary shares will be admitted to trading on the market of Euronext Growth and the issued ADSs will trade on Nasdaq.

On an illustrative basis, assuming the issuance of the full amount of $125.0 million of ADSs under the ATM program at an assumed offering price of $19.14, the last reported sale price of the ADSs on Nasdaq on March 26, 2021, a holder of 1.0% of the outstanding Company’s share capital as of the date of this press release, would hold 0.9% of the outstanding Company’s share capital after the completion of the transaction (calculated on the basis of the number of outstanding shares on the date of publication of this press release).

During the term of the ATM program, the Company will include in the publication of its quarterly results information about its use of the program during the preceding quarter and will also provide an update after each capital increase on a dedicated location on its corporate website in order to inform investors about the main features of each issue that may be completed under the ATM program from time to time.

A shelf registration statement on Form F-3 (including a prospectus) relating to Cellectis’ ADSs was filed with the SEC and became effective upon filing. Before purchasing ADSs in the offering, prospective investors should read the prospectus supplement and the accompanying prospectus, together with the documents incorporated by reference therein. Prospective investors may obtain these documents for free by visiting EDGAR on the SEC’s website at www.sec.gov. Alternatively, a copy of the prospectus supplement (and accompanying prospectus) relating to the offering may be obtained from Jefferies LLC, 520 Madison Avenue, New York, NY 10022 or by telephone at (877) 821-7388 or by email at [email protected]. No prospectus will be subject to the approbation of the Autorité des Marchés Financiers ("AMF").

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. In particular, no public offering of the ADSs will be made in Europe.

On March 29, 2021 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported that the European Commission (EC) has granted conditional marketing authorization for NEXPOVIO (selinexor), the Company’s first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) medicine, in combination with dexamethasone for the treatment of multiple myeloma in adult patients who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, two immunomodulatory agents, and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy (Press release, Karyopharm, MAR 29, 2021, View Source [SID1234577260]).

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!

Conditional marketing authorization is supported by data from the positive Phase 2b STORM study, which evaluated selinexor in adult patients with heavily pretreated, triple class refractory multiple myeloma and was published in the New England Journal of Medicine (Chari, et al.) in August 2019. Under the provisions of conditional approval by the EC, continued authorization for this indication is contingent upon verification and description of clinical benefit in a confirmatory trial and is subject to additional monitoring. An EC marketing authorization through the centralized procedure (CP) is valid in all 27 European Union (EU) member countries, as well as the European Economic Area (EEA) countries of Iceland, Liechtenstein and Norway.

"NEXPOVIO represents the first and only nuclear export inhibitor authorized in Europe and we are delighted to bring this new treatment option to eligible adult patients with heavily pretreated multiple myeloma. Despite advancements in the treatment of multiple myeloma, most adult patients will eventually relapse and develop disease that is refractory to all authorized therapies, further highlighting the urgent need for new therapies with novel mechanism of actions like NEXPOVIO," said Sharon Shacham, PhD, MBA, Founder, President and Chief Scientific Officer of Karyopharm. "Our first product authorization in Europe could not have been possible without the dedication of the patients, caregivers, physicians and Karyopharm employees involved in the clinical development of NEXPOVIO over the last 13 years."

"Today’s authorization is an important step forward in the international expansion of selinexor, now with marketing authorization for use in Europe, Israel and the U.S.," said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. "We are committed to making NEXPOVIO available in Europe initially through a Named Patient Program and are on track to submit a second European regulatory filing in April based on the positive data from the Phase 3 BOSTON study to potentially further expand NEXPOVIO to eligible adult patients in need of new treatment options."

About the Phase 2b STORM Pivotal Trial

The Phase 2b STORM trial (Selinexor Treatment of Refractory Myeloma) was an international, multi-center, single-arm, open-label study which enrolled 123 adult patients (Part 2 of the trial) with heavily pretreated, triple class refractory multiple myeloma. Adult patients in the trial had a median of seven previous therapeutic regimens, including a median of 10 unique anti-myeloma agents.

For the study’s primary endpoint, oral selinexor achieved an overall response rate of 26% (95% confidence interval [CI], 19, 35) and the trial therefore met its primary endpoint (n=123). Minimal response per IMWG criteria was observed in 16 (13%) patients and 48 patients (39%) had stable disease. All responses were adjudicated by an Independent Review Committee. Among the modified intent to treat population enrolled in STORM Part 2, eighty–three (83) patients had relapse and/or refractory multiple myeloma that was refractory to two proteasome inhibitors (bortezomib, carfilzomib), two immunomodulators (lenalidomide, pomalidomide) and an anti-CD38 monoclonal antibody (daratumumab), the efficacy analysis was based on these 83 patients. A secondary efficacy endpoint included overall survival (OS), defined as the duration from start of study treatment to death due to any cause. The median OS was 8.6 months in the total population (n=123) studied and 15.6 months in adult patients who had a minimal response or better.

Karyopharm’s request for conditional authorization in Europe was based upon the same patient population that served as the basis for XPOVIO’s accelerated FDA approval in the U.S. The overall response rate in this patient population (n=83) was 25.3 % (95% confidence interval [CI], 16.4, 36).

The most common adverse reactions in the STORM trial (≥20%) were thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of adult patients. Serious adverse reactions occurred in 58% of adult patients. Treatment discontinuation rate due to adverse reactions was 27%.

About Multiple Myeloma in Europe

Multiple myeloma (MM) is an incurable cancer with significant morbidity and the second most common hematologic malignancy. In 2020, there were approximately 51,000 new cases and 32,000 deaths from MM in Europe1. While the treatment of MM has improved over the last 20 years, and overall survival has increased considerably, the disease remains incurable, and nearly all adult patients will eventually relapse and develop disease that is refractory to all authorized anti-MM therapies. Therefore, there continues to be a high unmet medical need for new therapies, particularly those with novel mechanisms of action.

About NEXPOVIO (selinexor)

NEXPOVIO, which is marketed as XPOVIO in the U.S., is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. NEXPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). NEXPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. NEXPOVIO (selinexor) has been granted conditional marketing authorization by the European Commission in combination with dexamethasone for the treatment of multiple myeloma in adult patients who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, two immunomodulatory agents, and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy.

Therapeutic indication for NEXPOVIO in the EU as well as The EEA Countries of Iceland, Liechtenstein and Norway

NEXPOVIO is indicated in combination with dexamethasone for the treatment of multiple myeloma in adult patients who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, two immunomodulatory agents and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy.

SELECT IMPORTANT SAFETY INFORMATION
NEXPOVIO is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. See www.mhra.gov.uk/yellowcard for how to report side effects.

Contraindications: Hypersensitivity to selinexor.

Special warnings and precautions for use:

Recommended concomitant treatments
Adult patients should be advised to maintain adequate fluid and caloric intake throughout treatment. Intravenous hydration should be considered for adult patients at risk of dehydration.
Prophylactic concomitant treatment with a 5-HT3 antagonist and/or other anti-nausea agents should be provided prior to and during treatment with NEXPOVIO.

Haematology
Adult patients should have their complete blood counts (CBC) assessed at baseline, during treatment, and as clinically indicated. Monitor more frequently during the first two months of treatment.

Thrombocytopenia: Thrombocytopenic events (thrombocytopenia and platelet count decreased) were frequently reported in adult patients receiving selinexor, which can be severe (Grade 3/4). Adult patients should be monitored for signs and symptoms of bleeding and evaluated promptly.

Neutropenia: Severe neutropenia (Grade 3/4) has been reported with selinexor.
Adult patients with neutropenia should be monitored for signs of infection and evaluated promptly.

Gastrointestinal toxicity: Nausea, vomiting, diarrhoea, which sometimes can be severe and may require the use of anti-emetic and anti-diarrhoeal medicinal products.

Weight loss and anorexia: Adult patients should have their body weight, nutritional status and volume checked at baseline, during treatment, and as clinically indicated. Monitoring should be more frequent during the first two months of treatment.

Confusional state and dizziness: Patients should be instructed to avoid situations where dizziness or confusional state may be a problem and to not take other medicinal products that may cause dizziness or confusional state without adequate medical advice. Patients should be advised not to drive or operate heavy machinery until symptoms resolve.

Hyponatraemia: Adult patients should have their sodium levels checked at baseline, during treatment, and as clinically indicated. Monitoring should be more frequent during the first two months of treatment.

Tumour lysis syndrome (TLS): TLS has been reported in adult patients receiving therapy with selinexor. Adult patients at a high risk for TLS should be monitored closely. Treat promptly in accordance with institutional guidelines.

Fertility, pregnancy and lactation
Women of childbearing potential/contraception in males and females: Women of childbearing potential and male adult patients of reproductive potential should be advised to use effective contraceptive measures or abstain from sexual activity to prevent pregnancy during treatment with selinexor and for at least 1 week following the last dose of selinexor.

Breast-feeding: It is unknown whether selinexor or its metabolites are excreted in human milk. A risk to breast-fed children cannot be excluded. Breast-feeding should be discontinued during treatment with selinexor and for 1 week after the last dose.

Elderly population
Patients 75 years and older had a higher incidence of discontinuation due to an adverse reaction, higher incidence of serious adverse reactions, and higher incidence of fatal adverse reactions.

Undesirable effects
Summary of the safety profile
The most frequent adverse reactions (≥30%) of selinexor in combination with dexamethasone were nausea, thrombocytopenia, fatigue, anaemia, decreased appetite, decreased weight, diarrhoea, vomiting, hyponatraemia, neutropenia and leukopenia.
The most commonly reported serious adverse reactions (≥3%) were pneumonia, sepsis, thrombocytopenia, acute kidney injury, and anaemia.

Description of selected adverse reactions
Infections: Infection was the most common non-haematological toxicity. Upper respiratory tract infection and pneumonia were the most commonly reported infections with 25% of reported infections being serious and fatal infections occurring in 3% of treated adult patients.

Reporting of suspected adverse reactions
Reporting of suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

On March 29, 2021 Incyte (Nasdaq:INCY) reported that the European Commission (EC) has approved Pemazyre (pemigatinib) for the treatment of adults with locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement that have progressed after at least one prior line of systemic therapy (Press release, Incyte, MAR 29, 2021, View Source [SID1234577259]). The decision follows the positive opinion received from the European Medicines Agency’s Committee for Medicinal Products for Human Use in January 2021 recommending the conditional marketing authorization of Pemazyre.

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!

"Pemazyre’s approval is a crucial milestone for patients with FGFR2 positive cholangiocarcinoma. It is the first new treatment option to be made available to these patients in the EU in over a decade and has demonstrated a high rate of durable responses in a setting where historically there has been no effective standard of care," said Hervé Hoppenot, Chief Executive Officer, Incyte. "We now look forward to working with individual countries in Europe to ensure eligible patients can access this new treatment as soon as possible."

The EC decision is based on data from the FIGHT-202 study evaluating the safety and efficacy of Pemazyre in adult patients with previously treated, locally advanced or metastatic cholangiocarcinoma with documented FGF/FGFR status. Interim results from FIGHT-202 demonstrated that in patients harboring FGFR2 fusions or rearrangements (Cohort A [108 patients]), Pemazyre monotherapy resulted in an overall response rate (ORR) of 37 percent (primary endpoint) and a median duration of response (DOR) of 8 months (secondary endpoint) based on an independent central radiographic review. Pemazyre was generally well tolerated. Warnings and precautions for Pemazyre include high and low levels of phosphate in the blood, vision or eye problems, blood creatinine increase and for women who are pregnant, a risk of harm to the fetus.

"The data from the FIGHT-202 study has demonstrated the potential benefits that pemigatinib may have for eligible patients living with cholangiocarcinoma," said Eric Van Cutsem, M.D., Ph.D., Professor and Division Head of Digestive Oncology, University of Leuven (KUL) and University Hospitals Gasthuisberg, Leuven, Belgium. "Pemazyre offers a much-needed option to eligible patients that have only had few effective treatment options until today."

Cholangiocarcinoma is a rare cancer that forms in the bile duct. It is classified based on its origin: intrahepatic cholangiocarcinoma occurs in the bile duct inside the liver and extrahepatic cholangiocarcinoma occurs in the bile duct outside the liver. Patients with cholangiocarcinoma are often diagnosed at a late or advanced stage when the prognosis is poor1,2. In Europe, the incidence of cholangiocarcinoma ranges between 6,000 – 8,0003,4. FGFR2 fusions or rearrangements occur almost exclusively in intrahepatic cholangiocarcinoma, where they are observed in 10-16 percent of patients5,6,7.

"Historically, patients living with advanced cholangiocarcinoma have had very limited treatment options," said Helen Morement, CEO, AMMF – The Cholangiocarcinoma Charity. "We are encouraged to see new, targeted therapies starting to be approved in Europe, giving hope to those in desperate need of alternatives."

About FIGHT-202

The FIGHT-202 Phase 2, open-label, multicenter study (NCT02924376) is evaluating the safety and efficacy of Pemazyre – a selective fibroblast growth factor receptor (FGFR) inhibitor – in adult (age ≥ 18 years) patients with previously treated, locally advanced or metastatic cholangiocarcinoma with documented FGF/FGFR status.

Patients were enrolled into one of three cohorts – Cohort A (FGFR2 fusions or rearrangements), Cohort B (other FGF/FGFR genetic alterations) or Cohort C (no FGF/FGFR genetic alterations). All patients received 13.5mg Pemazyre orally once daily (QD) on a 21-day cycle (two weeks on/one week off) until radiological disease progression or unacceptable toxicity.

The primary endpoint of FIGHT-202 is overall response rate (ORR) in Cohort A, assessed by independent review per RECIST v1.1. Secondary endpoints include ORR; progression free survival (PFS), overall survival (OS), duration of response (DOR), disease control rate (DCR) and safety in all cohorts.

For more information about FIGHT-202, visit View Source

About FIGHT

The FIGHT (FIbroblast Growth factor receptor in oncology and Hematology Trials) clinical trial program includes ongoing Phase 2 and 3 studies investigating safety and efficacy of Pemazyre therapy across several FGFR-driven malignancies. Phase 2 monotherapy studies include FIGHT-202, as well as FIGHT-201 investigating Pemazyre in patients with metastatic or surgically unresectable bladder cancer, including with activating FGFR3 mutations or fusions/rearrangements; FIGHT-203 in patients with myeloproliferative neoplasms with activating FGFR1 fusions/rearrangements; FIGHT-207 in patients with previously treated, locally-advanced/metastatic or surgically unresectable solid tumor malignancies harboring activating FGFR mutations or fusions/rearrangements, irrespective of tumor type.

FIGHT-302 is a Phase 3 study investigating Pemazyre as a first-line treatment for patients with cholangiocarcinoma with FGFR2 fusions or rearrangements.

About Pemazyre (pemigatinib)

Pemazyre is a kinase inhibitor indicated in the United States for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test8. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

In Japan, Pemazyre is approved for the treatment of patients with unresectable biliary tract cancer (BTC) with a fibroblast growth factor receptor 2 (FGFR2) fusion gene, worsening after cancer chemotherapy.

In Europe, Pemazyre is approved for the treatment of adults with locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement that have progressed after at least one prior line of systemic therapy.

Pemazyre is a potent, selective, oral inhibitor of FGFR isoforms 1, 2 and 3 which, in preclinical studies, has demonstrated selective pharmacologic activity against cancer cells with FGFR alterations.

Pemazyre is marketed by Incyte in the United States, Europe and Japan. Incyte has granted Innovent Biologics, Inc. rights to develop and commercialize pemigatinib in hematology and oncology in Mainland China, Hong Kong, Macau and Taiwan. Incyte has retained all other rights to develop and commercialize pemigatinib outside of the United States.

Pemazyre is a trademark of Incyte Corporation.

Safety Information from the EU Summary of Product Characteristics (SmPC)

Pemazyre may cause serious adverse reactions. The most common serious adverse reactions were hyponatremia and blood creatinine increase.

The most common adverse reactions were hyperphosphatemia, alopecia, diarrhoea, nail toxicity, fatigue, nausea, dysgeusia, stomatitis, constipation, dry mouth, dry eye, arthralgia, hypophosphatemia, dry skin and palmar-plantar erythrodysaesthesia syndrome.

Prolonged hyperphosphatemia can cause precipitation of calcium-phosphate crystals that can lead to hypocalcemia, soft tissue mineralization, anemia, secondary hyperparathyroidism, muscle cramps, seizure activity, QT interval prolongation and arrhythmias. Soft tissue mineralization, including cutaneous calcification and calcinosis, have been observed with Pemazyre treatment. Recommendations for management of hyperphosphatemia include dietary phosphate restriction, administration of phosphate-lowering therapy and dose modification when required.

Pemazyre can cause serous retinal detachment reactions, which may present with symptoms such as blurred vision, visual floaters or photopsia. Ophthalmological examination, including optical coherence tomography (OCT) should be performed prior to initiation of therapy and every 2 months for the first 6 months of treatment, every 3 months afterwards, and urgently at any time for visual symptoms. For serous retinal detachment reactions, the dose modification guidelines should be followed.

Pemazyre should not be used during pregnancy unless the clinical condition of the women requires treatment with Pemazyre. Patients with cancer cells that have spread into the brain or spinal cord should notify their physician before initiating treatment with Pemazyre.