Top 10 Most Valuable Drug R&D Projects in Biopharmaceuticals: Insights from Evaluate’s EP Vantage Report

Compiled by | newborn

EP Vantage, a subsidiary of the globally renowned life sciences industry market consultancy Evaluate, recently released a report analyzing the top 10 most valuable new drug development projects in the biopharmaceutical sector. Below is a brief introduction to each drug.

1

Tirzepatide

This drug is a large-molecule polypeptide developed by Eli Lilly, functioning as a dual agonist of the glucose-dependent insulinotropic polypeptide (GIP) receptor and the glucagon-like peptide-1 (GLP-1) receptor. Both GIP and GLP-1 are gut-derived hormones that promote insulin secretion. Data presented at this year’s American Diabetes Association (ADA) Scientific Sessions demonstrated that, in patients with type 2 diabetes, the drug effectively lowered blood glucose levels while significantly reducing body weight and exhibiting an improved gastrointestinal side effect profile. Furthermore, the drug also improved markers associated with nonalcoholic steatohepatitis (NASH).

Data from the pivotal SURPASS program is expected to be released by the end of 2020. Eli Lilly also plans to advance another triple GIP/GLP-1/glucagon receptor agonist into Phase II clinical trials next year. Competitor Novo Nordisk is also developing new drugs with this mechanism, with Phase I data from NN1706 expected to be released soon. Existing data suggest that multi-receptor agonists demonstrate superior efficacy in glycemic control and weight reduction compared to pure GLP-1 agonists. Analysts have pointed out that multi-target receptor agonists will be a key focus in the diabetes field in 2020.

2

BMS-986165

This drug is a novel, oral, selective TYK2 inhibitor developed by Bristol Myers Squibb. Its unique mechanism of action differs from that of other kinase inhibitors. Currently, the drug is in Phase III clinical trials for the treatment of psoriasis and various autoimmune diseases. TYK2 is an intracellular signaling kinase that mediates cytokine-driven immune and pro-inflammatory signaling pathways, which play a crucial role in the chronic inflammatory cycle of immune-mediated diseases.

When discussing this drug, it is impossible not to mention Celgene’s other medication, Otezla. In late June, to secure approval from U.S. antitrust regulators, Bristol Myers Squibb (BMS) decided to divest Otezla, which Amgen acquired in October for $13.2 billion. For the treatment of psoriasis, Otezla is considered a safer but less effective option, and BMS believes that BMS-986165 holds greater commercial potential. Currently, Pfizer and Johnson & Johnson are also developing TYK2 inhibitors, making this novel mechanism a key area of focus in the field of autoimmune diseases in 2020.

3

TransCon hGH

This medication is a long-acting human growth hormone (hGH) developed by Ascendis for the treatment of pediatric growth hormone deficiency (GHD), a condition caused by insufficient secretion of growth hormone from the pituitary gland. Children with GHD not only exhibit short stature but also face metabolic abnormalities, psychosocial challenges, cognitive deficits, and reduced quality of life. For decades, the standard of care for GHD has been once-daily subcutaneous injections of hGH to improve growth and metabolic outcomes. The high treatment burden associated with daily injections poses significant challenges for caregivers and patients, leading to poor adherence and diminished overall therapeutic efficacy.

Developed using TransCon technology, this drug enables the sustained release of unmodified growth hormone at a predictable rate over one week; this growth hormone is identical to the once-daily hGH used in routine clinical practice. In Phase III clinical trials, weekly subcutaneous administration of this drug demonstrated superior efficacy compared to once-daily hGH (11.2 cm/year vs. 10.3 cm/year, p=0.0088). In 2018, Ascendis and Vivo Capital established a joint venture, Vigene Biosciences, to develop TransCon technology products in the Greater China region. This October, TransCon hGH received approval from the NMPA, initiating Phase III clinical studies in China.

4

Bempegaldesleukin（NKTR-214，bempeg）

This drug is an immunostimulant developed by Nektar Therapeutics. It is a CD122-biased IL-2 pathway agonist that stimulates the proliferation of anticancer immune cells in the body, including natural killer (NK) cells, CD4+ T cells, and CD8+ T cells, by targeting the CD122-specific receptors present on their surfaces. In preclinical studies, NKTR-214 demonstrated therapeutic potential across multiple tumor types.

Currently, Nektar has partnered with pharmaceutical companies such as Pfizer/Merck, Bristol Myers Squibb, Merck & Co., and Eli Lilly to evaluate bempeg in combination with immune checkpoint inhibitors for the treatment of various solid tumors. Among these, the combination of bempeg and Opdivo for the treatment of melanoma and renal cell carcinoma has entered Phase III clinical trials, while its application in urothelial carcinoma is in Phase II clinical trials. Data presented at the SITC annual meeting in November this year showed that the overall response rate of bempeg + Opdivo as first-line treatment for metastatic melanoma reached 53%.

5

SAGE-217

This drug, developed by Sage Therapeutics, is a next-generation positive allosteric modulator with enhanced selectivity for GABA receptors, which play a critical role in regulating the central nervous system. It is currently in Phase III clinical trials for the treatment of postpartum depression (PPD), major depressive disorder, treatment-resistant depression, and major depressive disorder comorbid with insomnia.

In early December this year, the Phase III clinical trial MOUNTAIN of SAGE-217 for the treatment of major depressive disorder failed, causing the company’s market value to drop by billions of dollars. However, industry analysts remain confident in the drug's potential for other indications, particularly PDD. In March this year, Sage Therapeutics’ drug Zulresso was approved by the U.S. FDA, becoming the first and only drug specifically approved for the treatment of PDD worldwide. However, while Zulresso is administered via intravenous infusion, SAGE-217 is taken orally. If approved, it will further solidify Sage’s dominance in the PDD field.

6

Tezepelumab

This drug, developed by Amgen, is a first-in-class anti-TSLP monoclonal antibody currently in Phase III clinical trials for the treatment of asthma. TSLP is an epithelial cytokine produced in response to pro-inflammatory stimuli and plays a key role in the initiation and persistence of airway inflammation. TSLP drives the release of downstream type 2 (T2) cytokines and can also activate various cell types involved in non-T2-driven inflammation. Due to its early upstream activity in the inflammatory cascade, TSLP has been identified as an important therapeutic target for broad-spectrum asthma treatment. Blocking TSLP prevents immune cells from releasing pro-inflammatory cytokines, thereby preventing asthma exacerbations and improving asthma control.

Currently, marketed biologic agents for asthma are indicated only for specific asthma phenotypes (i.e., patient subgroups), such as eosinophilic asthma. Tezepelumab specifically binds to human thymic stromal lymphopoietin (TSLP) and blocks its interaction with the receptor complex. By targeting an early upstream point in the inflammatory cascade, this drug has the potential to treat a broad population of patients with severe, uncontrolled asthma, regardless of phenotype or type 2 (T2) biomarker status. Previously, the U.S. Food and Drug Administration (FDA) granted tezepelumab Breakthrough Therapy Designation. If approved for marketing, the eligible patient population for this drug will be substantially larger than that for existing asthma biologics.

7

Mirikizumab

This drug, developed by Eli Lilly and Company, is a humanized IgG4 monoclonal antibody that targets the p19 subunit of IL-23. It is being developed for the treatment of various immune-mediated diseases, with Phase III clinical trials underway for psoriasis, ulcerative colitis, and Crohn's disease.

Currently, there are several IL-23 inhibitors on the market, including Johnson & Johnson’s Stelara and Tremfya, Sun Pharma’s Ilumya, and AbbVie’s Skyrizi. Among these four drugs, only Stelara is approved for Crohn’s disease. Some analysts believe that mirikizumab has the potential to become the fifth IL-23 inhibitor to enter the market in terms of psoriasis treatment. However, in immune-mediated intestinal diseases (including Crohn’s disease and ulcerative colitis), this drug has a greater opportunity to achieve breakthroughs, which will also be an important disease area for Eli Lilly's development.

8

mRNA-2752

Developed by the biotech “unicorn” Moderna, this innovative mRNA therapy converts immunologically unresponsive “cold” tumors into “hot” tumors. Administered via local (intratumoral) injection, mRNA-2752 encodes three immunomodulators: two secreted cytokines, IL-23 and IL-36γ, and a T-cell receptor membrane-bound costimulatory molecule, OX40L. The drug generates high concentrations of immunomodulators in the tumor microenvironment, thereby altering the “cold” tumor milieu, inducing a broad immune response, and promoting the elimination of both injected and distant tumors.

Although still in Phase I clinical trials, some bold analysts have already painted a bright and promising future for the drug. Notably, it is the only asset among the Top 10 that is currently in Phase I clinical development. In 2020, Moderna will release clinical data, which will help provide a clearer picture of the drug’s prospects.

9

Efgartigimod

This drug is an industry-leading anti-FcRn program developed by the Belgian pharmaceutical company Argenx. It is a first-in-class anti-FcRn antibody fragment utilizing ABDEG technology, which targets and binds to the IgG recycling receptor FcRn, thereby preventing IgG recycling. This mechanism accelerates IgG depletion and promotes IgG clearance. Currently, the drug is being developed for the treatment of various severe autoimmune diseases mediated by high levels of pathogenic IgG, such as myasthenia gravis (MG), immune thrombocytopenia (ITP), pemphigus vulgaris (PV), and chronic inflammatory demyelinating polyneuropathy (CIDP). Notably, its development for the treatment of myasthenia gravis (MG) has entered Phase III clinical trials. In Phase II clinical trials, efgartigimod demonstrated highly favorable efficacy data in the treatment of MG, ITP, and PV.

Notably, in the report “The 15 Most Valuable New Drug Development Assets Not Yet Partnered in 2018,” efgartigimod topped the list with a net present value of $6.4 billion. This November, Argenx issued 4.6 million ordinary shares, raising $550 million. This appears to signal that the company is determined to go it alone in the development of efgartigimod.

10

RG7828

RG7828 (mosunetuzumab) is a humanized, full-length T-cell-dependent bispecific antibody that targets CD20 on B cells and CD3 on T cells. This dual targeting activates and redirects the patient’s T cells to eliminate target B cells by releasing cytotoxic proteins into them. Currently, the drug is in Phase II clinical development for the treatment of various hematologic malignancies.

At the ASH Annual Meeting held this December, mosunetuzumab emerged as a focal point of industry attention—demonstrating robust and durable responses in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (R/R B-NHL) who have a very poor prognosis, including those who relapsed after CAR-T cell therapy. This represents a truly significant advancement that poses a tangible threat to more complex cellular therapies currently under development. Data presented at the meeting showed that the overall response rate (ORR) was 62.7% and the complete response rate (CR) was 43.3% in patients with indolent NHL; in patients with aggressive NHL, the ORR was 37.1% and the CR was 19.4%. Among patients who relapsed after CAR-T cell therapy, the ORR was 38.9% and the CR was 22.2%.

Reference source: Ones to watch: biopharma’s most valuable R&D projects