Clinical strategy, medical oversight and clinical due diligence

Alacrita's consulting team supports a number of pharmaceutical & biotech companies with medical and clinical strategy. We have particular depth in oncology, but also have expertise in infectious diseases (in particular novel antibiotics), autoimmune and respiratory diseases. Illustrative projects include:

• For a leading immuno-oncology biotech company with a pipeline of novel, first-in-class clinical stage assets, Alacrita provided medical support for multiple activities in Europe and the United States. These included clinical strategy and execution of the clinical development plans for the company's drug candidates, drug safety and pharmacovigilance, and the fostering of existing and future relationships with KOLs, medical advisors and medical advisory boards. Alacrita also assessed portfolio expansion  opportunities and other corporate development activities from a clinical development and medical perspective.
• For a listed biotech company conducting Phase III clinical trials in an oncology indication, Alacrita provided chief medical officer support for multiple clinical activities in Europe and the United States. These included medical oversight of three ongoing clinical trials, in particular preparation for marketing application, preparing for DSMB review of an ongoing Phase IIb clinical trial and preparing the launch of a Phase II clinical study in pancreatic cancer. Alacrita also provided medical oversight of a Phase I clinical trial.
• For a pharmaceutical company conducting due diligence on an in-licensing/acquisition candidate, Alacrita provided medical due diligence services for a Phase IIb respiratory drug. Alacrita's expert respiratory physician, who has a wealth of drug development expertise from both big pharma and biotech, reviewed the available documentation, including:
  • investigator brochure
  • clinical study reports and publications of data from two completed clinical studies in a target indication
  • clinical protocol and statistical analysis plan for the ongoing Phase IIb clinical trial.
  • feedback from the European Scientific Advice Working Party concerning paediatric development and from the FDA in response to an IND submission for the Phase IIb protocol.

We concluded that the ongoing Phase IIb would have, at best, modest improvement in clinical performance and the drug would likely generate significant adverse events. We advised the client that in-licensing of the product should only  be considered if the results provided more compelling evidence of clinical effectiveness than that available to date. The pharma company did not proceed with the transaction and the Phase II trial later failed to meet its primary endpoint.

Additional Pharmaceutical Consulting Projects:

I. Providing an independent review of data from a recently-completed clinical trial

Challenge: A small biopharmaceutical company asked Alacrita to provide an independent review of data from a recently-completed clinical trial and provide a summary report for the company’s management and board of directors.  This request had a tight timeline due to an upcoming board meeting – Alacrita had only six days from the initial transfer of data until the final report was to be submitted.

The clinical trial was a multinational phase 3 randomized study that had been conducted in patients with advanced colorectal cancer.   Alacrita received slide decks containing background information on the product and preliminary analyses from the company.  Other materials reviewed by Alacrita included the clinical trial protocol, statistical analysis plan, numerous SAS output tables and minutes from end of phase 2 meetings with FDA, EMA and PMDA.

Solution: Alacrita’s effort was led by a medical oncologist who has over 20 years of industry experience in clinical development. The Alacrita report included analysis and/or commentary on:

• the study population, baseline characteristics and imbalances between treatment groups
• patient disposition by treatment group
• drug exposure, adverse events and safety in each treatment group
• primary and secondary efficacy endpoints
• performance of the control arm in various subgroups and relative to historical data
• treatment effect in various subgroups, potential confounding variables and interpretation of Cox proportional hazard models
• recommendations for additional statistical analyses of the data set
• recommendations for new clinical studies that the company may want to consider
• recommendations on potential next steps with FDA and other health authorities
• comment on potential implications for the company’s discovery platform

The report was prepared and sent to the company 24 hours before the deadline.  This allowed the company’s management team to review the report and send follow up questions, which Alacrita answered (including additional data analyses) within three hours, allowing the management team to have the information prior to their board meeting.  The company’s board used this information to help them set direction for the company.

II. Providing due diligence on a start-up biotech

Challenge: A family-run investment firm was potentially interested in a foreign start-up biotechnology company. Through grant support, the biotech had identified a new oncology target and developed a peptide drug to activate that target. The drug was based on the normal interactions that happen between the target and a hormone-like protein found in the body. Encouragingly, early data suggested that this drug led to the death of cancer cells grown in culture. The drug had been through pre-clinical trials, and Phase I clinical testing had begun in patients with tumors that weren’t responding to the clinically available treatment regimens. The fledgling company was considering a Phase II trial in the near future to look for efficacy, and was seeking investors.

Our consultant had been specifically recommended to the client as being a thought-leader in early-stage oncology drugs. The client had previous exposure to technology companies through their real estate investments, but had not previously invested directly in biotechnology companies. They therefore sought an expert opinion of the product, the strength of the scientific data, and the potential for its future development.

Solution: Our consultant began with a review of the data that were publicly available data or provided by the biotechnology company. His assessment focused on:

• the nature of the target
• the strength of efficacy of the compound in pre-clinical models
• any safety concerns that arose from the pre-clinical and Phase I data
• an analysis of the robustness of the proposed Phase II trial

From this assessment, which included conversations with the Chief Scientific Officer of the biotechnology company, he concluded that there was limited evidence that the drug could overcome the development hurdles necessary for it to become clinically useful. Furthermore, there were some signals in the Phase I trial that suggested there could be safety concerns with the drug. He prepared a report outlining his findings, recommending that the investment firm search for opportunities other than this particular company. That report included industry benchmark data for success rates of oncology products at a similar stage of development, in order to put the biotechnology company’s outlook in context for these investors who had limited experience in such entities.

III. Assessing pharma company assets for potential development opportunities

Challenge: A recently founded private equity firm had a mandate to acquire the rights to sidelined products from pharmaceutical companies and develop them through to market. By focusing on products with relatively small potential target patient populations, the firm hoped to identify drugs that were far along the development pipeline and had substantial clinical potential, but that were not being pursued for business reasons or other factors. The firm’s founders had substantial experience in the pharmaceutical industry.

The firm approached Alacrita with their first serious candidate acquisition target, and asked us to help assess the drug’s clinical and commercial potential. This drug was already approved by the FDA and marketed for a very small group of patients – those with a slow-growing type of cancer that is not acutely life-threatening – and the pharmaceutical company had no further trials planned.

Solution: Firstly, our oncology-specialist consultant reviewed the publically available data and also determined the status of the numerous ongoing investigator-sponsored trials of the drug. From this information, he put together a life-cycle management plan that included additional trials that could be done in these areas as well as other diseases in which the drug could be effective, both of which would broaden the total potential market for the drug.

Meanwhile, Alacrtita’s commercial-specialist consultant conducted a similar assessment, including interviews with key opinion leaders who were familiar with the drug and the disease. His key questions included:

• how is the drug currently being used in clinical practice?
• are there any attributes of this drug that could help differentiate it from its competitors?
• how could these be highlighted in future clinical trials?
• what are the perceptions of the drug within the medical community?

Together, our consultants developed a 360 degree plan for the private equity firm that included:

1. A two-pronged clinical plan, consisting of (a) a potential label expansion, which could be done by collecting data from patients with a rare, inherited syndrome that predisposed these individuals to this type of cancer and (b) a trial of the drug in combination with other therapies, particularly surgery. This trial would be large and lengthy, so our consultants suggested collaborating with a cooperative group with a special interest in this tumor type that would be willing to spearhead this trial.
2. A roadmap for building a virtual organization to execute the drug development plan.
3. A business plan outlining a commercial organization that could provide marketing, sales, medical affairs and pharmacovigilance. The plan described key functionalities and ideas on staff recruitment.

IV. Assessing radiation oncology field for growth opportunities with immune oncology

Challenge: A major player in the radiation oncology market was looking for growth opportunities. It had identified cancer immunotherapy as a potential opportunity, given the increasing evidence that radiation can synergize with immunotherapy. Radiation, especially when delivered in the optimum way, can be immune stimulatory by increasing tumor antigen exposure, disrupting the tumor microenvironment and eliciting danger signals, all of which culminate in the tumor cells becoming an ‘in situ’ cancer vaccine. In particular, there was increasing clinical evidence of PD1 and radiation synergy, with several impressive complete responses documented in the literature. Alacrita was tasked with developing a strategy and business plan to help our client share in the value that this opportunity afforded.

Solution: We conducted an in depth review of the literature to understand the scientific and clinical evidence supporting radiotherapy and immunotherapy synergy. We then interviewed several key opinion leaders to supplement our findings from the literature, learn about any unpublished data and hear from them about the opportunities that may exist for our client.

Armed with a solid understanding of the field, we conducted a comprehensive review of the cancer immunotherapy development landscape to identify and prioritize potential assets and partnership opportunities for our client. We introduced our client to several immunotherapy companies and facilitated initial discussions to gauge the mutual interest in a collaboration.

We developed a database of all radiation/immunotherapy combination clinical trials that were currently ongoing, detailing the relevance, stage of development, principal assets under investigation and other key parameters. We supplemented this with a summary database of the literature we had identified and reviewed.

We then set out several recommendations for our client, which helped the company build an internal business case for board approval. These included building internal capabilities and expertise in cancer immunotherapy, initiation of R&D collaborations with selected academic labs, biotech and pharma companies. We developed detailed budgets for these activities and showed, through rNPV modeling and comparables analyses, how our client could secure a significant financial return on these investments.

For additional case studies or to find out how our life science consulting expertise can assist your project, please contact us.