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Can These Breakthrough Therapeutics win the fight against Mesothelioma?

26 Feb Can These Breakthrough Therapeutics win the fight against Mesothelioma?

An estimated 2,400 – 2,800 new incidence of Mesothelioma occurs each year in the U.S alone, according to an estimate by the Centers for Disease Control and Prevention (CDC). The disease caused by exposure to asbestos will likely affect 20 million people worldwide according to a research. Over 91% of all diagnosis occur in patients aged 55 or older and is more common in men than women, more likely due to occupational exposure.

The treatment options available are chemotherapy, surgery and radiotherapy. One of the biggest challenges in treating Mesothelioma is its long latency period, delayed prognosis and indistinguishable symptoms. The survival rates of Mesothelioma patients are improving owing to advancements in the treatment options such as immunotherapy and cytoreductive surgery plus HIPEC.

A rising geriatric population, increasing pollution levels and improved diagnostic tools are likely to drive the growth in the industry. Long latency period and low surveillance rate along with non-availability of effective treatment could derail the growth in the market according to a report titled “Malignant Mesothelioma Treatment Market – Global Industry Analysis, Size, Share, Growth, Trends and Forecast 2017 – 2025 by transparencymarketresearch.com. The market is expected to reach US$ 604 million by 2025 with a CAGR of 7.5% according to an estimate by persistence market research.

The Mesothelioma treatment industry is geared towards major changes with increased public awareness and a favorable government and regulatory environment paving way for innovative approaches to tackling the disease. The focus is now on development of combination therapies involving the use of chemotherapy and immune-oncology procedures and below mentioned are some companies which are at the forefront of innovation in this field.

TCR2 Therapeutics (NASDAQ: TCRR)

Market Cap: $364.54M; Current Share Price: 15.72 USDChart

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Its proprietary TRuC (TCR Fusion Construct) utilizes the power of T cell signaling pathways and receptors to eliminate cancer cells. This clinical stage immunotherapy company intends to use its T cell therapies to treat hematologic cancers and solid tumors.

Image Source: https://www.tcr2.com/our-approach

Its technology is driven by the TCR complex and phosphorylation motifs (ITAMs) that can bind to tumor antigens and catalyze a complex signaling cascade that can annihilate cancer cells. It’s TRuC™ Platform is an optimal amalgamation of the CAR-T and TCR-T cell therapies minus their shortcomings. It overcomes the limitations of the existing treatment options such as inability to target solid tumors, severe cytokine release syndrome, increased neurotoxicity, HLA down regulation and lack of HLA matching.

The company’s clinical data has shown its superior anti-tumor ability over CAR-T cells with minimal levels of cytokines. It has also demonstrated faster migration to the tumor, improved metabolic fitness and enhanced tumor penetration as compared to CAR – T. Its non-dependence on HLA matching allows it to be used for a larger patient population as well as introduction of improvements to include targeting multiple tumor antigens simultaneously, reduction in treatment expenditure by using off-the-shelf allogenic cells, and accessories to overcome the suppressive effect of the tumor microenvironment.

The company’s lead drug candidate TC-210 was granted an Investigational New Drug (IND) status by the FDA in January 2019. Preparations are underway for a phase I/II Clinical trials to be initiated in Q1, 2019. Its pipeline has an impressive line-up of drug candidates targeting multiple conditions such as ovarian cancer, pancreatic cancer and hematological malignancies.

Image Source: https://www.tcr2.com/our-approach

In recognition of its efforts, the company was conferred with the U.S. Private Company of the Year Award at LifeStars Awards TM Life Sciences 2018 Event in November 2018.

Image Source: Company presentation

The company has numerous strategic collaborations with research partners such as Fred Hutch, UNI Freiburg, Massachusetts General Hospital and University of Pittsburgh. Its investing partners include 6 Dimension capital, Arrowmark, Cathay Fortune Corp, Curative Ventures, Hillhouse Capitals, F2, MPM and Redmile group to name a few.

The company raised $125 million through a Series B financing in March 2018. It recently announced an initial public offering of 5,000,000 shares of common stock at a public offering price of $15.00 per share, for total gross proceeds of $75.0 million, before deducting underwriting discounts and commissions and offering expenses as per a company release.

Epizyme (NASDAQ: EPZM)

Market Cap: $956.75M; Current Share Price: 12.09 USDChart

Data by YCharts

Epigenetics is at the core of its novel therapeutic inventions for treatment of cancer and other serious illnesses and the company is pioneering the development of small molecule inhibitors of histone methyltransferases (HMTs), histone acetyltransferases (HATs) and helicases. It is focused on creating oral medication that can target specific diseases and offer ease of administration and tolerability. Presently, three out of its five novel epigenetic therapies are in clinical development stage and two are in pre-clinical stage.

Its lead drug candidate, tazemetostat, is being developed for the treatment of cancer using its platform of new epigenetic target classes that are crucial in disease biology. Its line-up of clinical candidates consists of novel small molecule programs for new disease targets such as EZM8266, a potential treatment of sickle-cell disease.

Image Source: http://www.epizyme.com/programs/product-platform/

Epizyme has entered into key strategic collaborations with companies such as Boehringer Ingelheim, Genentech (a member of the Roche Group), Lymphoma Study Association (LYSA), EISAI Co. Ltd. (TYO:4523), Celgene Corporation (NASDAQ:CELG) and GlaxoSmithKline plc (NYSE:GSK) for advancing the development of its drug candidates as well as leveraging on a range of research and development programs. It has received over $200 million in non-equity funding till date due to these agreements. As part of its arrangements with EISAI, it has retained the global rights to tazemetostat, an EZH2 inhibitor outside of Japan for an upfront payment of $40 million and consideration of future royalties, while with Celgene it has commercialization rights in the United States for two of their programs namely DOT1L (Acute leukemia) and pinometostat (EPZ-5676) for $65 million in upfront payment and an equity investment of an additional $25 million besides royalty and milestone payments in the future.

It’s collaboration with Boehringer Ingelheim is for enzymes within the helicase and histone acetyltransferase (HAT) families whose dysfunction has been linked to the development of cancers.  Genetech and Epizye have an agreement to study the combination of tazemetostat and Genentech’s approved anti-PD-L1 cancer immunotherapy, Tecentriq™ (atezolizumab), for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), the most common form of non-Hodgkin lymphoma (NHL).

LYSA and its collaboration are for the investigation of its tazemetostat with R-CHOP, a standard chemotherapy for NHL, as a front-line treatment in elderly, high-risk patients with newly diagnosed DLBCL. GSK paid an upfront payment of $20 million with research, development and regulatory milestone payments of up to $402 million and sales-based milestone payments of up to $218 million in the offing for its novel small molecule HMT inhibitors.

The company reported gross proceeds of $86.25 million on account of its underwritten public offering of 9,583,334 shares of its common stock at a public offering price of $9.00 per share. At the end of Q3, 2018, its cash, cash equivalents and marketable securities were $180.8 million as against $307.2 million as of September 30, 2017.

Aldeyra Therapeutics (NASDAQ: ALDX)

Market Cap: $202.08M; Current Share Price: 7.70 USDChart

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Aldeyra’s lead product candidate is reproxalap, a small molecule RASP (Reactive Aldehyde Species) inhibitor that can be used in the treatment of dry eye disease, allergic conjunctivitis, noninfectious anterior uveitis, and Sjögren-Larsson Syndrome. It is also developing other drug candidates for cancer, autoimmune diseases, post-transplant lymphoproliferative disease and retinal inflammation.

Image Source: https://www.aldeyra.com/our-novel-platform/

It seeks to leverage its understanding of Reactive Aldehyde Species (RASP) levels to tackle intracellular inflammatory factors including NF-kB, a prominent protein in the inflammatory response. Its reproxalap can bind to free aldehydes triggering a covalent reproxalap-aldehyde adducts that can degrade intracellularly within hours with significant lowering of aldehyde levels.

Image Source: Company

In the pipeline are drug candidates ADX-1612 for Mesothelioma, PTLD and Ovarian cancer, ADX-629 and ADX-1615 for autoimmune disorders that are undergoing clinical trials. It announced positive top-line results from its Phase I/II clinical trials for ADX-1612 (ganetespib) in patients with pleural malignant mesothelioma named MESO-2, which showed improved partial response rates when combined with standard pemetrexed and platinum therapy. It is in preparation of phase II trials pending its discussion with regulatory authorities.

As per the company’s press release, “The MESO-2 results are highly encouraging. Addition of ADX-1612 to pemetrexed and either cisplatin or carboplatin achieved an overall response rate of 61%, the highest seen to date for addition of a novel agent to front-line chemotherapy,” said Professor Dean Fennell MD PhD, Chief Investigator of the Cancer Research UK MESO-2 clinical trial. “Hsp90 inhibition could represent a new advance for the treatment of mesothelioma.”

It raised funds amounting to $67.6 million through its underwritten public offering in October 2018.  As of September 2018, its cash, cash equivalents, and marketable securities balance stood at $35.1 million.

Atara Biotherapeutics (NASDAQ: ATRA)

Market Cap: $ 1.75B; Current Share Price: 38.37 USDChart

Data by YCharts

A pioneer in the T-cell immunotherapy space, Atara offers rapid delivery of Off-the-shelf bioengineered allogeneic T cells from donors with healthy immune function for the treatment of cancer, autoimmune and viral diseases. These can target cancerous and disease-causing cells with precision and eliminate them with minimal collateral cell damage. Most importantly, there is no need for lymphodepletion before treatment.

The company is leveraging its decade long clinical experience at Memorial Sloan Kettering (MSK) by using cell selection algorithm to identify the most appropriate T-Cell lines by matching key immune characteristics.

Its lead product candidate for mesothelioma is ATA2271 that uses a novel CAR T 1XX co-stimulation and CAR T PD-1 DNR, which is in preclinical stage. A MSK sponsored Phase 1 study (NCT02414269) of a mesothelin-targeted CAR T immunotherapy is currently under progress with emphasis on development of a next-generation, mesothelin-targeted CAR T using novel 1XX CAR signaling and PD-1 dominant negative receptor (DNR) checkpoint inhibition technologies. The company has exclusive licensed global rights to a mesothelin-targeted chimeric antigen receptor T-cell (CAR T) immunotherapy for solid tumors from Memorial Sloan Kettering Cancer Center (MSK) as per a company press release.

Image Source: https://www.atarabio.com/pipeline/preclinical-programs/

The company has created T-Cells to recognize EBV and CMV Viral antigens and the tumor associated antigen, Wilms tumor 1 (WT1) using technology licensed from MSK and developed product candidates namely ATA129, ATA230, and ATA520. It has a licensing agreement with QIMR Berghofer for the use of its T-Cell technology that can target selective antigen for specific EBV, CMV, HPV, and BK viral antigens and is developing product candidates ATA188, ATA621, ATA368, and ATA274 on the basis of this technology.

Image Source: https://www.atarabio.com/science-and-technology/next-generation-car-t-technologies/

The company is fully focused on CAR T opportunities and is developing numerous next generation and off-shelf technology options that cover a gamut of targets and diseases, overcome resistance and have an improved safety profiles. It has collaboration with Moffitt Cancer Centre and MSK to develop multi-targeted CAR T Immunotherapies.

Image Source: https://www.atarabio.com/wp-content/uploads/2017/08/AtaraBio_21Aug2017_web_CTLmanu-1.jpg

The company has a state of the art expandable ATOM (Atara T-Cell Operations and Manufacturing) facility in California which is currently completing licensure for clinical production to confirm to global regulatory standards.

Atara has a strong pipeline of product candidates in clinical development stage such as Tab-cel® (tabelecleucel) for treatment of hematologic and solid tumors, Solid Tumors, Acute Myeloid Lukemia, B-Cell Malignancies, Autoimmune disease and Infectious disesase CAR T programs to name a few.

As per the company’s Q3, 2018 financial results, cash, cash equivalents and short-term investments as of September 30, 2018 totalled $364.5 million.


Market Cap: $ 3.44B; Current Share Price: 107.95 USDChart

Data by YCharts

This biotechnology company is a pioneer in field of therapeutic antibodies and has an innovative proprietary technology platform based on antibody capabilities and peptide formats. Its lead product candidate MOR208, a lenalidomide combination in relapsed/refractory diffuse large B cell lymphoma (r/r DLBCL) has been awarded a breakthrough therapy designation by the FDA. The company boasts of a vast pipeline of products consisting of over 29 product candidates by virtue of various proprietary and partnership agreements.

Image Source: https://www.morphosys.com/sites/default/files/phone-conferences/downloads/190121_mor_company_update_incl_appendix.pdf

The company has built a robust partnership and collaboration network to achieve growth and advancement in multiple areas such as cancer, psoriasis, alzheimer’s solid tumors, hemophilia and inflammation to name a few.

Image Source: https://www.morphosys.com/sites/default/files/phone-conferences/downloads/190121_mor_company_update_incl_appendix.pdf

Its proprietary development pipeline consists of its lead product candidate MOR208 targeted at DLBCL (B-MIND) and is in phase III clinical trials, while its MOR107 for oncology is in preclinical stage. It is developing MOR202 for multiple myeloma in partnership with I-Mab Biopharma for development in China, Hong Kong, Macau, Taiwan and South Korea (MOR210 only) and MOR210 for oncology applications, the company has received a $20 million upfront and is eligible for another $100 million in milestone payments and tiered double-digit royalties.

It has collaboration with Novartis (NYSE:NVS)/Galapagos (NASDAQ:GLPG) for development of MOR106 for treatment of atopic dermatitis for which the company has received EUR 95 million and will receive an estimated EUR 850 million in milestone payment in the future along with royalties.

It is also developing MOR103 /GSK3196165, an anti – GM-CSF antibody for inflammatory diseases in a full out-licensed agreement with GSK in lieu of EUR 22.5 million upfront payment and potential milestone payments of EUR 423 million and royalties.

The company successfully raised $208 million through its IPO listing in April 2018.










Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.

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