Biotecnol – Developing Cutting-Edge Therapeutic Approaches to Fight Cancer

Many cancer patients and caregivers may be familiar with traditional treatments, such as chemotherapy and radiation. Several important features of immunotherapy, a form of cancer treatment that uses the power of the body's immune system to prevent, control and eliminate cancer, make for a more specific answer to cancer. Immuno-oncology is a rapidly evolving and complex field that offers great potential to deliver substantial benefits to patients with a range of different cancers. A number of approved therapies already exist that offer impressive and long lasting responses in some patients. Clinical studies on long-term overall survival have shown that the beneficial responses to cancer immunotherapy treatment are durable—that is, they may be maintained even after treatment is completed.

Biotecnol is a private biopharmaceutical company working in the field of immuno-oncology. Biotecnol develops highly-specific antibody-based immunotherapies which activates and directs the defenses of a patient's own immune system, such as their own Killer T-Cells (T-lymphocytes that kill cancer cells) to fight various types of cancers where standard of care treatments have shown little or no benefit. Biotecnol Limited, a spin-off of Biotecnol SA, a Portuguese pioneering company with a 20 year track record in development of Biologics, is an immuno-oncology company developing immune-function activating and immuno function modulation approaches using multi-specific antibody products based on its proprietary Tribody^™ and Trisoma^® technologies.

Biotecnol’s Tribody^™ Technology

The Tribody ^™ technology enables the generation of multi-specific antibody products. This unique technology overcomes the key shortcomings of conventional mono- as well as of currently developed bi-specific antibody formats. With the Tribody^™ technology, Biotecnol can engineer and assemble recombinant antibodies in a rational manner in order to design a chosen mechanism of action to address the killing of a specific tumor type. An anti-CD3 antibody which binds the T-cells is engineered in the Tribody^™ "scaffold" where additional tumor antigens are also engineered.  These molecules are generated via the natural in vivo heterodimerization of Fab fragments to form a scaffold (the process carried out in just one reaction in vivo and there is neither chemical nor any other means of conjugation or attachment), upon which three specific antibodies are incorporated. The resulting molecules are stable and easy to produce in a single batch, without the need of additional post-production reactions other than purification. Tribodies are successfully produced in standard mammalian cell technology (CHO technology) using well-established methods.

Trisoma^®: Helping Fight Cancer with Iron Fist

Trisoma^® is a high-throughput, powerful and well-controlled platform based on proprietary methods and protocols for generating and characterizing a Tribody™ candidate drug substance. The Trisoma^® platform is used for the assembly, engineering and testing of various Tribody™ molecules with various distinct properties under various structural formats with optimal stability and desired pharmacological properties in terms of bioavailabity.

Under the Trisoma^® platform, Biotecnol has developed a novel format known as "Targeted T-cell Engaging Agonistic Response Modifiers" or iChecks™. These products aim at improving tumor cell dependent T-cell or NK-cell activation. The iCheck™ formats are expected to achieve a more localized immune-function activation and obtain less or no systemic toxicity, whilst having an increased therapeutic index.These are potentially safer and more effective drugs for treating highly-heterogeneous and highly-aggressive solid tumors. Biotecnol is constantly improving on the engineering of the Trisoma^® platform and its associated technology in order to build new intellectual property and optimize the characteristics of such versatile Tribody™ derived molecules.

Biotecnol’s Robust Product Suite

Biotecnol is developing its products, up to and including clinical proof of concept in man through development milestones that represent key value inflection points with the aim of subsequently license or selling them to a pharmaceutical partner. The company is designing various products, some under collaborations with undisclosed partners. The company is committed to explore the design of treatments using combinations of novel agents in this exciting, dynamic and constantly emerging space of cancer immunotherapy, which could contribute significantly to fighting highly heterogeneous and aggressive cancers. Biotecnol has various undisclosed candidates being tested both in solid and non-solid tumors. Furthermore, these products are being investigated as dual-targeting agents, making the most out of the trispecific features of the versatile Tribody™ Platform.

Tb535: Biotecnol’s First product moving to the clinic trials

Tb535 is a T-cell engager Tribody™ with a pan-cancer application potential for treating solid tumors expressing 5T4/WAIF1. Tb535 is Biotecnol's first candidate entering clinical development in a collaboration with Cancer Research UK (CRUK). Tb535 is a Tribody™, against the well-validated oncofoetal tumor-associated antigen, 5T4/WAIF1, originally isolated from trophoblasts. The 5T4/WAIF1 tumor antigen is a protein found on many different solid tumors and is thought to contribute to the spread of cancer cells.  Tb535 binds to the tumor antigen on the surface of the tumor cell. Upon accumulation of Tb535 it triggers primed CD8+ CTLs, to engage and kill the target tumor cells.

5T4/WAIF1 is expressed on a majority of solid tumors including colorectal (40-80%), renal (>95%), breast (85-90%), ovarian (70%), Malignant Mesothelioma (98%), gastric (50-70%), non-small cell lung (>99%), prostate (>80%) and cervix (86-90%) cancers.  Expression of 5T4/WAIF1 on a patient tumor cells is a negative prognostic factor in several malignancies. Furthermore, 5T4/WAIF1 expression has been associated with the cancer stem cell phenotype. By contrast, expression levels of 5T4/WAIF1 in normal tissues generally absent or are very low. Immunohistochemistry of normal tissues from healthy donors showed no 5T4/WAIF1 staining in major tissues (adrenal, blood, marrow, breast, brain, colon, heart, kidney, liver, uterus cervix, lung, lymph nodes, pancreas, parathyroid, prostate, skin, spinal cord, spleen, muscle, testis, thyroid, stomach, ileum or eye). Clear positive staining was found in placenta only. Weak expression was seen in some samples of normal bladder, fallopian tube, endometrium, pituitary, ureter and duodenum.

A two-center open label, dose escalation clinical study for evaluation of the tolerability and safety of Tb535, in various patients with tumors expressing 5T4/WAIF1 is planned. The study will assess safety, maximum tolerated dose (MTD), recommended phase two dose, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity including biomarkers of anti-tumor activity. It will be a dose escalation study to establish a recommended dose and schedule, for the continued clinical development of Tb535.

The Mastermind behind the Success of Biotecnol

Pedro de Noronha Pissarra, Ph.D. is the Chief Executive Officer of Biotecnol.  He has over 20 years of experience in the Biotechnology Industry and his entrepreneurial activities are internationally acknowledged. Pedro has built over the years an extensive track-record in growing early stage projects in healthcare.

Pedro holds a B.Sc. and a Ph.D. in Biotechnology from Kings College London (University of London). He carried out research at several institutions, including the Chemical Engineering Department of Massachusetts Institute of Technology (M.I.T.), Cambridge, USA and at the Centre for Process Biotechnology (CPB) of the Technical University of Denmark, Lyngby, Denmark. Following his Doctoral degree he specialized in medical sciences and oncology. After his Postdoctoral training he undertook a 12 month Master’s Program in Management at the IC2 Institute of the University of Texas, Austin, USA.

Pedro has been awarded the Medal of Merit by the Oeiras Council in Portugal in recognition for his role in promoting entrepreneurship and for services provided to the council of Oeiras (Portugal), where Biotecnol SA, the biotechnology pioneer company in Portugal started its operations and is present since 1996.

“Biotecnol’s strategy is to work with top cancer institutions in the immune-oncology field which will help the company to accelerate the development of cutting-edge therapeutic approaches to fight cancer.”