In-depth inventory: Dynamic panorama of anti-cancer drug research and development in 2022 (January-April)

▎ WuXi AppTec content team editor

Cancer is one of the most concerned areas of disease. From the perspective of the burden of disease, cancer causes nearly 10 million deaths each year, accounting for nearly one-sixth of the total number of deaths in the world, and there is a huge unfinished medical need. From the perspective of annual new drug approvals, in the past five years, the largest number of innovative therapies approved by the FDA is also for the treatment of cancer, accounting for nearly 30% of the new drugs approved each year. In today's article, WuXi AppTec's content team will combine the approval of new drugs, regulatory updates, and clinical progress from January to April this year to provide readers with the latest anti-cancer drug development trends.

Content Overview

A total of 5 new anti-cancer therapies were approved for the first time

A total of 4 innovative cancer therapies have been qualified as FDA breakthrough therapies, of which 3 have not yet been approved

A total of 7 innovative anti-cancer therapies have been qualified for FDA priority review, of which 2 have not yet been approved

A total of 17 anti-cancer therapies received positive Phase 3 clinical trial results within the statistical range or submitted marketing applications

A total of 10 overseas cancer-fighting companies have received financing of $50 million or more

In the R&D news of progress, the most common target is still PD-1, followed by HER2

In the R&D news of progress, the number of news related to small molecule drugs, monoclonal antibodies, and antibody-conjugated drugs is tied for the first place

Among overseas emerging companies with a Series A financing of not less than $50 million, 30% focus on innovative cell and gene therapies, 20% on molecular gum degradation therapies, and 20% on new immunotherapies

Note: The statistical interval is from January to April 2022

Approved new drugs

Between January and April this year, the U.S. FDA approved a total of twelve new drugs, four of which were used for cancer treatment, accounting for one-third, close to historical data. There are many highlights in these four new drugs, including the first approved TCR therapy and the first approved LAG-3 antibody. During the same period, China's NMPA also approved a number of innovative anti-cancer therapies, of which the anti-PD-1 monoclonal antibody from Henlius has not been approved in other countries and regions around the world.

Kimmtrak（tebentafusp-tebn）

Immunocore

Kimmtrak was approved in January this year to treat specific uveal melanoma. As an innovative bispecific protein, Kimmtrak consists of a fusion of two parts: a soluble T cell receptor with high affinity at one end, and an immune effector domain against CD3 at the other. This therapy specifically targets gp100, an antigen expressed in melanocytes and melanoma. The approval set a number of firsts: It was the first FDA-approved treatment for unresectable or metastatic uveal melanoma. It is also the first regulatory-approved T cell receptor (TCR) therapy and the first FDA-approved bispecific T-cell junction for the treatment of solid tumors.

Vonjo（pacritinib）

CTI BioPharma

Vonjo was approved in February to treat patients with myelofibrosis, a type of bone marrow cancer, with severe thrombocytopenia. Pacritinib is a novel oral kinase inhibitor that specifically inhibits JAK2, IRAK1 and CSF1R. Because it does not target JAK1, the potential side effects of inhibiting JAK1 can be avoided.

Opdualag (nivolumab and relatlimab)

Bristol-Myers Squibb

The "first-in-class" therapy Optualog, approved in March, consists of a fixed dose of the anti-LAG-3 antibody drug relatlimab combined with the anti-PD-1 antibody Opdivo (nivolumab) to treat adults and children (12 years of age and older) with unresectable or metastatic melanoma. It is worth mentioning that relatlimab is the first LAG-3 antibody approved by the US FDA, and the first innovative cancer immunotherapy approved for a new immune checkpoint in the past decade. Clinical data show that patients with initially treated metastatic or non-resectable melanoma receiving nivolumab monotherapy have a moderate progression-free survival of 4.6 months (95% CI: 3.4 to 5.6). The median PFS of patients receiving combination therapy was significantly prolonged at 10.1 months (95% CI: 6.4 to 15.7). This is the first treatment option in metastatic melanoma that also has a statistical benefit relative to anti-PD-1 antibody monotherapy.

Pluvicto（lutetium Lu 177 vipivotide tetraxetan）

Novartis

Also in March of this year, Novartis' targeted radioligand therapy Pluvuicto was approved to treat patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer. In recent years, radiopharmaceuticals have become an important direction in the field of precision treatment of tumors. Novartis' Pluvuicto links small molecule compounds that bind to PSMA with radioactive isotopes. It binds to prostate cancer cells expressing PSMA and kills tumor cells through the radiant energy released by radioisotopes, triggering cell death. It is also the first targeted radioligand therapy approved by the FDA for the treatment of such patients.

Hans-like (Srolizumab, serplulimab)

FuHong Henlin

Hans is Henlin's first self-developed innovative biologic drug approved by NMPA in March for indications for advanced solid tumors in adults with unresectable or metastatic microsatellite highly unstable (MSI-H) treatments that have failed previous standard treatments. The indications for pan-cancer species are also expected to bring new treatment options to more patients. Applications for the therapy combined with chemotherapy for advanced or metastatic squamous non-small cell lung cancer have also been accepted and are expected to be approved this year.

Breakthrough Therapies and Priority Reviews

From January to April this year, four anti-cancer therapies were recognized as breakthrough therapies by the US FDA. From the perspective of the diseases treated, there are three types of non-small cell lung cancer, reflecting that research and development in this field is still hot. In terms of the type of therapy, traditional small molecule drugs and new antibody-coupled drugs (ADCs) account for half of each. It is worth mentioning that three of the four innovative therapies that have been identified as breakthrough therapies have not yet been approved for marketing. They promise to bring entirely new treatment options to patients around the world in the future.

Telisotuzumab vedotin

Abbvie

Telisotuzumab vedotin

The fastest-growing ADC project in the EberWich pipeline, the drug targets c-Mets with the tubulin inhibitor MMAE as a toxic payload for the treatment of advanced/metastatic EGFR wild-type nonsquamous non-small cell lung cancer with advanced/metastatic EGFR wild-type nonsquamous non-small cell lung cancer that develops during or after platinum drug therapy. For this particular patient group, there are currently no approved effective anti-cancer therapies. Interim analysis of a Phase 2 clinical trial showed that the overall response rate (ORR) was 53.8% in the high-expression group of c-Met and 25.0% in the group with medium c-Met expression among eligible subjects.

CLN-081

Cullinan Oncology

CLN-081

is an irreversible oral next-generation small molecule EGFR inhibitor that selectively targets cells carrying the EGFR exon 20 insertion mutation without affecting wild-type EGFR-expressing cells. This therapy promises to treat patients with treated non-small cell lung cancer with EGFR exon 20 mutations. In a Phase 1/2a clinical trial, developers are evaluating the efficacy and safety of CLN-081 at different doses.

DZD9008

Di Zhe Pharmaceutical

DZD9008

is an innovative small molecule compound designed for EGFR/HER2 exon 20 insertion mutations, with the preferred indication for the treatment of non-small cell lung cancers carrying EGFR exon 20 insertion mutations. As of July 30, 2021, global clinical trial results show that DZD9008 has confirmed the best objective response rate (ORR) of 45.5% and 41.9% at 200 mg/day and 300 mg/day, respectively, and has shown efficacy in both patients with brain metastases and patients with poor or post-treatment treatment.

Between January and April, a total of seven anti-cancer therapies were granted priority review by the U.S. FDA, most of which were previously approved therapies for further indications. The blockbuster antibody-conjugated drug Enhertu, brought by AstraZeneca/13, has also once again come into the spotlight, winning a total of two priority evaluation qualifications. Of the therapies that have not yet been approved, one targets FGFR1-4 and the other targets CTLA-4.

Futibatinib

Taiho Oncology

Japan's Taiho Pharmaceutical and its subsidiary Taiho Oncology announced in March that the U.S. FDA had accepted a new drug application (NDA) from futibatinib for the treatment of patients with locally advanced or metastatic cholangiocarcinoma with FGFR2 gene rearrangement, including gene fusion. Futibatinib is a potently selective irreversible small molecule inhibitor of FGFR1, 2, 3, 4. FDA also granted this application priority review and expects to respond by September 30 this year. The application is based on data from a critical Phase 2b clinical trial in which 103 patients were treated with futibatinib. The primary endpoint of the clinical trial was the objective response rate (ORR), the ORR of futibatinib was 41.7%, the key secondary endpoint was the duration of remission (DOR), the median DOR of futibatinib was 9.7 months, and 72% of patients who received remission had DOR of more than 6 months.

Tremelimumab / Imfinzi

AstraZeneca

In April this year, AstraZeneca's application for the licensing of biological products submitted by the CTLA-4 antibody tremelimumab was accepted by the US FDA and will be reviewed through the priority review channel, and is expected to receive a response in the fourth quarter of this year. The therapy will be combined with the anti-PD-L1 antibody Imfinzi (durvalumab) to treat patients with unresectable hepatocellular carcinoma. In a Phase 3 clinical trial, the risk of death was reduced by 22% compared with the active control group in patients treated with this regimen (HR 0.78, 96.02% CI, 0.65-0.93, p=0.0035). Nearly one-third (31%) of patients survived more than 3 years, compared with 20% in the active control group.

Expected future listings

In addition to the several therapies mentioned above, there are also a number of anti-cancer drugs that have also made positive progress between January and April this year – either submitting new drug applications or achieving positive Phase 3 clinical results. Going forward, these innovative therapies are also likely to come out smoothly and benefit more patients.

Momelotinib

Sierra Oncology

In January, Sierra Oncology announced that its potent, investigative selective oral JAK1, JAK2, and ACVR1 inhibitors, momelotinib, met all major and key secondary endpoints in a critical Phase 3 clinical trial for the treatment of patients with myelofibrosis: more patients in the momelotinib group met the overall symptom score (TSS) below baseline by more than 50 percent compared to the placebo group. Based on these positive results, the company plans to file a New Drug Application (NDA) with the U.S. FDA in the second quarter of this year.

Mirvetuximab soravtansine

ImmunoGen

ImmunoGen released the results of a key Phase 3 clinical trial of antibody-conjugated drugs (ADCs) mirvetuximab soravtansine that target folic acid receptor α (FRα) in March. The results of the trial showed that in patients with treated advanced ovarian cancer who were resistant to platinum-containing therapy, mirvetuximab monotherapy showed clinically significant anti-tumor activity, consistent safety and good tolerability. Based on the results obtained so far, the company has submitted a biological product licensing application (BLA) for the drug to the US FDA in the same month.

I131-omburtamab

Y-mAbs Therapeutics

Y-mAbs Therapeutics filed a biological license application (BLA) for radioimmunotherapy I131-omburtamab with the U.S. FDA in April for the treatment of neuroblastoma in children. Omburtamab is a monoclonal antibody under investigation that targets the immune checkpoint molecule B7-H3, which is widely expressed in several types of cancer cells. By binding radioactive iodine (I131) to antibodies that target B7-H3, it is possible to reduce toxicity to healthy cells while killing cancer cells. In a key Phase 2 clinical trial, 10 children achieved a 90% disease control rate after 26 weeks of treatment, including two patients in partial response and two patients in complete response.

I/ONTAK

Citius Pharmaceuticals

Citius Pharmaceuticals announced in April that it had achieved positive top-line results in a critical Phase 3 clinical trial of the study therapy I/ONTAK for the treatment of patients with persistent or recurrent cutaneous T-cell lymphoma. I/ONTAK is a recombinant fusion protein that binds the IL-2 receptor binding domain to a diphtheria toxin fragment. It can specifically bind to IL-2 receptors on the surface of cells, causing diphtheria toxins to enter cells and inhibit protein synthesis. This therapy kills cancerous T cells and temporarily removes regulatory T cells (Treg), thereby enhancing the anti-cancer immune response. In one study, the Independent Review Committee assessed the therapy to achieve an objective response rate of 36.2% (95% CI, 25.0%, 48.7%). Based on this result, the company expects to file a biological product licensing application with the US FDA in the second half of this year.

KN046

Corning Jerry

In March this year, Corning Jereh announced that its first Phase 3 clinical study of PD-L1/CTLA-4 dual antibody KN046, which was developed in its own right, had completed its first interim analysis and reached a preset endpoint. In the first mid-term analysis conducted by the Independent Data Monitoring Board, KN046 plus platinum-containing chemotherapy compared with placebo plus platinum-containing chemotherapy achieved significant and clinically significant progression-free survival (PFS) prolongation in patients with advanced squamous non-small cell lung cancer in patients with advanced squamous non-small cell lung cancer based on the evaluation of the blind independent imaging review committee in the intentional therapy (ITT) population. Based on this result, Corning Jerry will submit a new drug application for KN046 for this indication as planned, combined with chemotherapy first-line treatment for squamous non-small cell lung cancer.

Early investment and financing progress

If we look to the longer term, what breakthrough innovations are sprouting that are expected to grow into towering trees in the future? Let's look to the up-and-coming companies that have received large amounts of early-stage funding this year. Cancer breakthroughs that belong to the future may come from among them.

TRIANA Biomedicines

Series A $110 million

Headquartered in Massachusetts, USA, TRIANA Biomedicines is a molecular gum research and development company, and its research and development strategy aims to focus on the target, using artificial intelligence (AI) technology to select ligases for each target, rationally design and discover molecular glue.

Ambagon Therapeutics

Series A $85 million

Headquartered in California, Ambagon Therapeutics aims to target protein targets traditionally considered "incurable" by developing molecular gums that stabilize the structure of intrinsically disordered proteins. Many disease-associated proteins carry intrinsic disordered regions that conventional small molecule drugs cannot target, but proteins with such intrinsic disordered regions, such as Raf protein kinase, FOXO transcription protein, and p53 cancer-driving cancer, can interact with adaptor proteins called 14-3-3. When binding to regions of disordered proteins, 14-3-3 proteins can induce the disordered proteins that bind to it to form a stable structure, giving them medicinal properties.

CDR-Life

Series A $76 million

Founded in 2017 and headquartered in Switzerland, CDR-Life is a cancer immunotherapy research and development company dedicated to the development of cancer immunotherapy that targets major histocompatibility complexes (MHCs) using antibody technology. CDR-Life's primary drug candidate, CDR404, is a antibody fragment-based, MAGE-A4-specific T cell engager. Another CDR-Life drug candidate, CDR101, a trispecific antibody that targets the B-cell maturation antigen (BCMA), is being developed to treat multiple myeloma (MM).

Pheast Therapeutics

Series A $76 million

Pheast Therapeutics' technology originated in the lab of Professor Irv Weissman, a renowned scholar at Stanford University. The company is committed to developing innovative anti-cancer therapies that target innate immune checkpoint proteins that regulate macrophage function. Most current immunotherapies enhance the adaptive immune response to cancer by targeting T cells. Pheast Therapeutics' unique strategy focuses on enhancing the innate immune response by targeting macrophage immune checkpoint proteins that prevent macrophages from engulfing tumor cells, commonly known as the "don't eat me" signal. The company found CD24 to be a new "don't eat me" signal. CD24 is highly expressed in a variety of tumors, especially ovarian and breast cancers. Blocking the CD24 signal allows the tumor to be recognized by macrophages and engulfed.

ArriVent Biopharma

Series A $69 million

Headquartered in Pennsylvania, USA, ArriVent Biopharma is a cancer targeted therapy research and development company. Through strategic collaborations with innovative biopharmaceutical companies, ArriVent aims to globalize pharmaceuticals, with the company's initial strategic focus on the field of oncology. Vometinib is the first drug candidate for ArriVent Biopharma and is licensed by Iris Pharma. The drug was approved in China in March 2021 for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with positive EGFRT790M mutations.

Rondo Therapeutics

Series A $67 million

Rondo Therapeutics is an antineoplastic drug development company dedicated to the development of bispecific antibodies. The company's bispecific platform hopes to enable the treatment of solid tumors by stimulating multiple downstream immune pathways. At the same time, Rondo is committed to creating a molecular "toolbox" that enables immune cells to be fully activated and produce differentiated molecules with the potential for a combination of monodrug activity and potential "best-in-class."

Alterome Therapeutics

Series A $64 million

Alterome Therapeutics, headquartered in San Diego, USA, is a precision oncology biopharmacy company. The company focuses on cancer research and hopes to develop effective targeted therapies for solid tumors such as colorectal cancer, non-small cell lung cancer and stomach cancer.

Indapta Therapeutics

The A round exceeds $50 million

Headquartered in California, Indapta Therapeutics is developing anti-tumor natural killer (NK) cell therapies. Indapta Therapeutics' technology platform can isolate and amplify a subset of NK cells called G-NK cells. Because G-NK cells have very active antibody-dependent cell-mediated cytotoxicity, their combination with monoclonal antibodies may bring significant clinical benefits to patients. These G-NK cells are isolated from healthy donors, do not require genetic engineering, and can be used as "ready-to-use" therapies to overcome the challenges of autologous T cell therapy in terms of therapy consistency.

Cimeio Therapeutics

Series A $50 million

Headquartered in Switzerland, Cimeio Therapeutics is a gene-editing and cell therapy research and development company dedicated to developing new therapies for rare genetic diseases, malignant blood tumors and autoimmune diseases. Cimeio Therapeutics' initial focus was on hematopoietic stem cell (HSC) transplantation and adoptive cell therapy (ACT), while using gene editing techniques to insert protein variants into HSCs or other types of cells to maintain cell function.

Kelonia Therapeutics

Series A $50 million

Kelonia Therapeutics plans to use the funds available to develop ready-to-use in vivo gene therapies, which will initially use lentiviral vectors to precisely deliver transgenes expressing chimeric antigen receptors (CAR) to generate CAR-T cell therapies in vivo, increasing the effectiveness of CAR-T therapies while avoiding the toxicity associated with traditional CAR-T therapies and complex production processes. The company's delivery platform can be used not only to produce cell therapies in vivo, but also to deliver other gene therapies, gene editing systems, or genetically modified organisms that regulate mRNA expression.

Future outlook

From the anti-cancer drugs approved this year, to the innovative anti-cancer therapies that may be approved in the short term, to the anti-cancer breakthroughs that may occur in a few years or even more than a decade, we can clearly see that innovative therapeutic molecular types are occupying an increasingly important position. From small molecules and antibody therapies, to the rise of antibody-coupled drugs, to protein degradation technologies such as molecular gums, and the emergence of cell and gene therapies, the field of cancer treatment can be described as a hundred flowers, not only bringing more treatment options to patients, but also bringing more development options to researchers. As Dr. Michael Mendelsohn, CEO of Cardurion Pharmaceuticals, said at the 2022 WuXi AppTec Health Industry Forum, if we can understand the targets and pathways behind diseases and find ways to discover and validate targets, then no matter what type of molecular type of treatment is used, it can bring breakthroughs to patients. We also look forward to the early arrival of this day.

Disclaimer: WuXi AppTec's content team focuses on the global biomedical health research process. This article is for informational purposes only and the views expressed herein do not represent the position of WuXi AppTec, nor do they represent WuXi AppTec's support for or opposition to the views expressed herein. This article is also not recommended for treatment options. For guidance on treatment options, please visit a regular hospital.

Copyright note: This article is from WuXi AppTec content team, welcome to forward to the circle of friends, refuse the media or institutions to reprint to other platforms in any form without authorization. Reprint authorization, please reply to "Reprint" on the "WuXi AppTec" WeChat public account to obtain the reprint instructions.

Share, like, watch, focus on global biomedical health innovation