The Antibody Society

the official website of the antibody society

An international non-profit supporting antibody-related research and development.

Amivantamab granted FDA approval for non-small cell lung cancer

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On May 21, 2021, U.S. Food and Drug Administration approved Rybrevant (amivantamab-vmjw) as the first treatment for adult patients with non-small cell lung cancer (NSCLC) whose tumors have specific types of genetic mutations: epidermal growth factor receptor (EGFR) exon 20 insertion mutations. Rybrevant received Priority Review and Breakthrough Therapy designation for this indication.

Amivantamab (JNJ-61186372; Janssen Pharmaceutical Companies of Johnson & Johnson) is a human, low-fucose IgG1-based bispecific antibody targeting EGFR and mesenchymal epithelial transition factor (MET) that was created using Genmab’s DuoBody technology. Amivantamab has been shown to function through multiple mechanisms of action in preclinical models of NSCLC with EGFR exon 20 insertion driver mutations, which cause tumor cells to be insensitive to EGFR tyrosine kinase inhibitors.

The efficacy of amivantamab was evaluated in a study of 81 patients with non-small cell lung cancer and EGFR exon 20 insertion mutations whose disease had progressed on or after platinum-based chemotherapy. In the trial population in which all patients received the drug, the overall response rate was 40% and the median duration of response was 11.1 months, with 63% of patients having a duration of response of 6 months or more.

FDA’s review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For review of amivantamab, the FDA collaborated with the Brazilian Health Regulatory Agency and United Kingdom’s Medicines and Healthcare products Regulatory Agency.

Need help keeping up to date on US and EU approvals?

The Antibody Society maintains a comprehensive table of approved monoclonal antibody therapeutics and those in regulatory review in the EU or US. The table, which is located in the Web Resources section of the Society’s website, can be downloaded in Excel format.

Funding the Development of Antibody Innovations, Part 1: Entrepreneurial Antibody Scientists

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By Tom Burt (Partner, Sofinnova Partners) & Nick Hutchinson (BSG Lead, Mammalian Cell Culture, FUJIFILM Diosynth Biotechnologies)

The Antibody Society has partnered with Tom Burt, Partner at Sofinnova Partners, a leading European venture capital firm in life sciences, specializing in healthcare and sustainability to produce a 4-part series of articles explaining the basics of financing a start-up biotech company. Our aim is to support and inspire researchers working in labs with a passion for their science and the drive to push their ideas as far as they will go. In Part 1, we discuss the characteristics of the entrepreneurial antibody scientist.

As of 2021, the pipeline of therapeutic antibodies is strong and the biopharmaceutical industry is enjoying unprecedented success in bringing new products to market (1). The launch of new antibody drugs can have a tremendous impact on the lives of patients suffering from diseases for which there are either no existing treatments or current treatments are lacking. Technological developments, such as Fc engineering, bi- and multi-specific antibody formats and antibody-drug conjugates will lead to improved antibody treatments in the future. Not all advances in antibody science are new drugs, however, and many are leading to new enabling research tools and novel diagnostics. The amount of innovation in the sector, driven by creative scientists working in labs around the world, is startling.

Scientists developing antibody therapeutics must progress the idea through discovery and development phases, including preclinical and clinical testing, with various regulatory hurdles that must be navigated before commercial launch can take place. Large pharma and biotech companies are well versed in managing the complexity and costs of antibody development and commercialization, but there is always room in the market for smaller, more agile players who can compete on an equal footing with these giants.

Entrepreneurial scientists are eschewing the traditional career pathways of staying in academia or joining large pharma companies (2) in favor of establishing their own companies. They are raising money to finance discovery and development, while managing their biotech businesses in order to turn their ideas into a reality. By adopting this approach, founders can retain much greater control of their inventions, can align the development of their technology with their own values, and furthermore, stand to benefit financially if their candidate is shown to be successful.

“It’s an excellent time to be considering raising finance for biotech start-ups. Investors have lots of capital that is waiting to be deployed and society is re-considering how it values medtech innovations in light of the pandemic,” explained Tom.

Investors’ attitudes to these different types of start-up will vary depending on the size of the investment that the company will need, the level of risk associated with the investment, the size of the likely return and the time it will take to see a return. Raising finance for different types of antibody start-up companies will depend on the business model and the nature of the innovation being commercialized. A technology for antibody discovery embedded in a piece of equipment will differ from an amino acid sequence that can be licensed, which will differ from an antibody therapeutic requiring ten years and hundreds of millions if not billions of dollars before any revenues are generated.

“Investors in therapeutics are very wary of “one-trick ponies” with only a single drug candidate,” says Tom. “We look for companies with innovative technologies that might be applied to a number of candidates for multiple disease targets. This reduces risks by ensuring the start-up can have multiple shots on goal.”

One such example is the start-up antibody company Gigagen, which was recently acquired by Grifols, a specialist in plasma-derived medicine. Gigagen’s Magnify Platform enables the identification of rare novel targets within the tumor microenvironment, which in turn can be fed into its Surge Platform, allowing the production of recombinant polyclonal antibodies derived from mammalian repertoires. The company has an oncology pipeline containing monoclonal and bispecific antibodies and a recombinant polyclonal immunoglobulin pipeline, which includes treatments for COVID-19 and other infectious diseases.

Like other start-up biotechs, Gigagen had licensed these platforms technologies to other antibody discovery and development companies in order to generate early revenues, before using them as a springboard to launch their own candidate development programmes.

In the next three posts in this series, we’ll explain the start-up financing cycle and how it relates to antibody companies, especially those developing antibody products for therapeutic use. We’ll use industry examples to describe different types of investors in antibody innovations, what they look for in a company or idea, and their expectations as to how the funding is utilized. We will also explain how the funding cycle is changing, which will help inventors fund the clinical journey more easily.

Watch for our second post next week!

1.       Kaplon H & Reichert JM (2021) Antibodies to watch in 2021. mAbs.

2.       Friedman J. How Biotech Startup Funding Will Changing in the Next 10 Years.

 

AIRR Community and Tsinghua University discuss Chinese research using AIRR-seq data to study adaptive immune response in COVID-19 patients

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A meeting focusing on Chinese researchers’ use of AIRR-seq data to study the adaptive immune response – especially in COVID-19 patients – was held recently by the AIRR Community and Tsinghua University.

The purpose of this co-organized meeting was to expose AIRR-seq researchers in China to the philosophy and tools developed by the AIRR Community and help integrate researchers from all over the world through the AIRR Community.

Although collaboration and sharing data internationally is complicated and difficult, this successful meeting was an important step in forming the relationships necessary for overcoming many of these challenges.

Tsinghua University is a major research university in Beijing and a member of the C9 League of Chinese universities. Since its establishment exactly 110 years ago, it has produced many notable leaders in science, engineering, politics, business, academia, and culture. The university is ranked as the 15th best university in the world in the QS World University Rankings and No.1 in Asia by the Asia University Rankings and the U.S. News and World Report.

The meeting followed a hybrid format, combining online lectures by AIRR Community members in the US and Europe in conjunction with an in-person meeting in Shenzhen, China that was organized by Professor Xiao Liu of Tsinghua University’s Shenzhen campus.

The in-person, all-day meeting was held on December 6, 2020 in Shenzhen, which corresponded to Saturday evening December 5 in North America.

The full meeting agenda can be found on the meeting web page and the meeting recording has been posted on the AIRR-C YouTube Channel.

 

Congratulations to the Antibody Engineering & Therapeutics Europe poster competition winners!

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To recognize the research activities of promising student/postdoctoral fellows, The Antibody Society sponsors a competition each year for members who submit posters for Antibody Engineering & Therapeutics Europe. This conference will be held virtually June 8-10, 2021.
Our judges select the best work based on originality, relevance and perceived impact on the field of antibody research and development.

 

Winners receive:

1) Complimentary registration to attend the conference and pre-conference sessions;
2) An opportunity to give a short oral presentation of their work in one of the conference sessions;
3) A lovely crystal award.

We are pleased to announce the winners of the 2021 poster competition:

Ms. Suchada Niamsuphap, Australian Institute for Bioengineering and Nanotechnology.

Poster title: Development of antibody delivery systems against intracellular targets

and

Dr. Vaishali Verma, University of Delhi South Campus.

Poster title: ImPACT: Immunization-free Phage-based Antibody Cloning Technology

More about these winners and the winners of past competitions can be found here.

Please join us for the virtual Antibody Engineering & Therapeutics Europe conference on June 8-10 to hear their presentations!

Society members receive a 15% discount on the registration fee. Contact us at membership@antibodysociety.org for the code.

Antibody therapeutics for melanoma

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May is Melanoma Awareness Month, with awareness campaigns kicking off on the first Monday (May 3rd in 2021). Melanoma is caused by cancerous melanocytes, which are cells in the epidermis that normally make a pigment, melanin, that protects other skin cells from damaging sun rays. The American Cancer Society (ACS) estimates the lifetime risk for developing the disease is ~ 2.6% (1 in 38) for whites, and 0.6% (1 in 167) for Hispanics, and 0.1% (1 in 1,000) for Blacks. Overall, melanoma is more common in men, and the risk of melanoma increases with age. The ACS’ data suggest that ~ 106,110 new melanomas will be diagnosed (~62,260 in men and 43,850 in women) and ~ 7,180 people may die of the disease in the United States during 2021.

Approved antibody therapies for melanoma

Three antibody therapeutics (ipilimumab, nivolumab, pembrolizumab)  that target the immune checkpoints CTLA-4 (CD152) or programmed cell death protein 1 (PD-1, CD279) are approved for melanoma.

  • YERVOY (ipilimumab), which targets cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), is indicated for the treatment of unresectable metastatic melanoma in adults and pediatric patients (12 years and older) and adjuvant treatment of patients with cutaneous melanoma with pathologic involvement of regional lymph nodes of more than 1 mm who have undergone complete resection, including total lymphadenectomy.
  • KEYTRUDA (pembrolizumab), which targets PD-1, is indicated for the treatment of patients with unresectable or metastatic melanoma, and for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.
  • OPDIVO (nivolumab), which targets PD-1, is indicated for the treatment of patients with unresectable or metastatic melanoma and disease progression, including following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor, and for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Combination therapy was shown to be superior to monotherapy with these checkpoint inhibitors in the Phase 3 Checkpoint study, which evaluated nivolumab monotherapy or nivolumab combined with ipilimumab versus ipilimumab monotherapy in patients with previously untreated unresectable or metastatic melanoma. The overall survival (OS) at 5 years was 52%, 44% and 26% in the nivolumab-plus-ipilimumab, nivolumab monotherapy, and ipilimumab monotherapy groups, respectively. However, Grade 3 or 4 treatment-related adverse events occurred more frequently in patients who received combination therapy (59%, 23%, and 28% of patients in the nivolumab-plus-ipilimumab, nivolumab, and ipilimumab treatment groups, respectively).

Investigational antibody therapies for melanoma

While the antibody therapeutics that target CTLA-4 and PD-1 have benefited melanoma patients, biopharmaceutical companies are developing novel antibody therapeutics that target other immune checkpoints such as LAG-3 or use different mechanisms of action.

  • Bristol-Myers Squibb is developing relatlimab (BMS-986016), which is a human IgG4 antibody targeting LAG-3 on T cells, thereby restoring effector function of exhausted T cells. Primary results from the Phase 2/3 RELATIVITY-047 (CA224-047) trial evaluating the fixed-dose combination of relatlimab and Opdivo (nivolumab) versus Opdivo alone in patients with previously untreated metastatic or unresectable melanoma indicated that the trial met its primary endpoint of progression-free survival.
  • Philogen  S.p.A. is developing Nidlegy, which is composed of two single-chain variable fragment (scFv)-based immunocytokines that target extra-domain B of fibronectin (L19IL2 + L19TNF combination), as neoadjuvant intralesional treatment for melanoma patients with locoregional disease. Two randomized, controlled Phase 3 registration trials for intralesional application of Nidlegy as a neoadjuvant followed by surgery + eventual adjuvant treatments (standard of care) and compared to standard of care are currently ongoing in Europe (PIVOTAL; NCT02938299) and in the USA (Neo-DREAM; NCT03567889) in patients with fully resectable stage IIIB/C melanoma.
  • Immunocore Ltd is developing tebentafusp, which comprises a high- affinity T cell receptor specific to a peptide sequence from the gp100 antigen, which is presented on melanoma tumor cells by HLA-A2, fused to an anti-CD3 single chain antibody fragment. In a Phase 3 study, tebentafusp demonstrated a statistically significant and clinically meaningful improvement in OS as a first-line treatment in metastatic uveal melanoma.  Tebentafusp has been granted Breakthrough Therapy Designation, Fast Track designation and orphan drug designation by the FDA and Promising Innovative Medicine designation under the UK Early Access to Medicines Scheme for metastatic uveal melanoma. Immunocore will be working with the FDA to complete submission of a BLA for tebentafusp in the third quarter of 2021.

The Antibody Society continuously collects data for antibody therapeutics in the commercial clinical pipeline. We will provide updates on the antibody therapeutics being evaluated for melanoma in future posts.

Need help keeping up to date on US and EU approvals?

The Antibody Society maintains a comprehensive table of approved monoclonal antibody therapeutics and those in regulatory review in the EU or US. The table, which is located in the Web Resources section of the Society’s website, can be downloaded in Excel format.