Biotech focus

Pivot Pharma’s PBDs Target DNA Damage & Genomic Instability to Treat Cancer

There are many different approaches to treating cancer, but the most difficult types to treat have emergent drug resistance properties. With few treatment options, researchers have begun to focus on these cancers given the limited competition along with the possibility of fast-tracked approval from the U.S. Food & Drug Administration. Novel Pyrrolobenzodiazepine dimers (PBDs) from Pivot Pharmaceuticals Inc. (OTCQB: PVOTF) represent one of the most promising types of therapeutics in the space.

What are PBDs?

Novel PBDs developed by Pivot Pharmaceuticals are distinct from previous generation PBDs. They have been shown in early preclinical studies to cause DNA replicative stress and/or disrupt the DNA damage response, and based on preclinical data hold great promise for anti-tumor activity in ‘genetically resistant’ cancers, including metastatic endometrial cancer, metastatic colorectal cancer, and triple-negative breast cancer. 

The development of these novel PBDs is planned through two distinct research and development strategies: 1) as small molecule drugs administered in combination with other chemotherapeutic agents; and 2) by conjugating these novel PBDs to various antibodies to create new antibody-drug conjugates (ADCs) to allow more targeted therapy options.  By binding to very specific sites in the DNA of a target cell, the agent effectively blocks the cancer cells’ division without distorting its DNA helix. This helps avoid the emergent drug resistance that renders many cancer therapeutics ineffective over time. 

What’s the Market Worth?

PBD therapies are expected to be most effective against ‘genetically resistant’ cancers that exhibit emergent drug resistance properties. For example, metastatic endometrial cancer affects about 50,000 patients with a market worth over $250 million while triple-negative breast cancer affects 40,000 patients with DNA repair deficiencies in a market worth over $200 million in the U.S. alone. These numbers could be much higher for similar cancer types and global populations.

Large pharmaceutical companies have begun to realize the benefit of PBD-based therapies. In April 2016, AbbVie (ABBV) acquired Stemcentrx - a PBD-ADC-focus oncology biotech firm - for $5.8 billion in cash and stock. The move follows AstraZeneca’s (AZN) acquisition of Spirogen - a similar developer of PBD-ADC focused therapeutics - back in October 2013. Many other pharmaceutical companies have started their own in-house PBD programs.

In addition to these acquisitions, there are several publicly traded companies developing novel drugs that have impressive market capitalizations.




Market Cap

Axovant Sciences Ltd.


Late Clinical

$2.65 B

Therapeutics MD Inc.


Late Clinical

$1.24 B

Myovant Sciences Ltd.


Phase II

$719 M

Lion Biotechnologies Inc.


Early Clinical

$424 M

Finally, many other chemotherapies and DNA-targeted agents have generated significant revenue before patent expiration. Abraxane generated nearly $700 million in 2013 sales, and Taxotere generated nearly $3 billion in 2009 sales for Sanofi-Aventis.  Topotecan, a chemotherapy agent for treatment of small cell lung cancer in patients that had failed to respond to initial treatment, had US sales of $140 million in 2010. These numbers demonstrate the blockbuster potential for such treatments in the cancer therapeutics space.

Pivot Pharma’s Opportunity

Pivot Pharmaceuticals Inc. aims to leverage chemistry and biology expertise from its acquisition of IndUS Pharmaceuticals, which has exclusive worldwide rights to a portfolio of PBDs from a research institution in India, coupled with biology and drug development expertise from the United States. The bi-continental development strategy provides significant cost-arbitrage opportunities and isn’t driven by a technology platform or process/infrastructure. This yields a low-cost, high-value opportunity for investors within the promising PBD space.

Currently, the company owns the intellectual property rights to three chemical entities, including PVT-005, PVT-006, PVT-007, targeting metastatic endometrial cancer, triple-negative breast cancer, metastatic colorectal cancer, and leukemias. Management plans to bring PVT-005 to market by 2021 and PVT-006 to market by 2022 with interim results serving as a potential catalyst for the company’s stock price in the meantime.

The company’s stock trades at a fraction of the value of other companies active in the PBD space despite its promising clinical programs and unique development approach. Axovant Sciences Ltd. (AXON), for example, trades with a nearly $3 billion market capitalization with late-stage programs while Lion Biotechnologies Inc. (LBIO) trades with a $424 million market capitalization with an early-stage clinical program.

Looking Ahead

Pivot Pharmaceuticals Inc. (OTCQB: PVOTF) represents a promising opportunity in the oncology space with a PBD-focused pipeline of therapeutics. Management aims to leverage the chemistry and biology platform from its acquisition of IndUS Pharmaceuticals to yield a cost-effective pathway to bring new anticancer drugs to the market, targeting several multi-million dollar indications with blockbuster-potential drugs.

For more information, visit the company’s website at