How Small Biotechs Can Overcome Study Execution Challenges and Achieve Big Results

Irit Gliko-Kabir, BioLineRx’s Vice President of Clinical Operations

Tanya du Plessis, Chief Data Strategist and Solutions Officer, Bioforum

Small-to-mid-size pharma and biotech companies are responsible for much of the innovation we’re seeing in the industry, developing much of the new drugs approved by the FDA in recent years. However, these organizations face a range of challenges and unique hurdles along the path to regulatory approval. From more complex molecules to more specialized product profiles to limited budgets and resources, these often-intertwined challenges can be difficult to navigate. However, they don’t have to limit success for an emerging company.

The recent and transformational success of the team at BioLineRx, a late clinical-stage biopharma focused on oncology, is a great example. In May 2021, BioLineRx announced positive top-line results of the groundbreaking GENESIS Phase 3 trial, evaluating its lead clinical candidate, Motixafortide, in combination with granulocyte colony stimulating factor (G-CSF, the standard of care in this indication), for hematopoietic stem-cell mobilization for autologous bone marrow transplantation in multiple myeloma patients. “An analysis of data on all 122 enrolled patients (the intent to treat, or ITT, population) found highly statistically significant evidence across the primary and all secondary endpoints favoring Motixafortide in addition to G-CSF, as compared to placebo plus G-CSF.” The addition of Motixafortide to G-CSF also allowed 88.3% of patients to undergo transplantation after only one apheresis session, compared to 10.8% in the G-CSF arm – an 8.2-fold increase, an important breakthrough for multiple myeloma patients and the healthcare providers who treat them.

I recently spoke with Irit Gliko-Kabir, BioLineRx’s Vice President of Clinical Operations, to learn more about BioLineRx’s journey developing a potential standard-of-care mobilization agent for autologous bone-marrow transplantation. She shared insights on how small, emerging companies can overcome challenges associated with their size and limited scale and efficiently, while maintaining the highest levels of quality, reach key clinical development milestones along the path to developing life-saving therapies.

1. How do the needs of smaller biopharma or biotech differ from those of larger life sciences organizations? What measures has BioLineRx put in place to address these specific needs?

Irit: For a smaller biopharma organization, time is especially valuable. We must be both professional and efficient to execute the clinical studies according to the planned timelines and maintain the highest levels of quality, with a limited buffer. The project management must be highly professional and precise, and there are multiple details and activities to stay on top of, which evolve along with the project. We accomplished this by creating a network of experts and strategic partners with the right experience to guide and support the BioLineRx team. Additionally, when outsourcing, communicating and aligning on expectations are essential, particularly around KPI planning and execution.

BioLineRx has found great success in outsourcing partnerships with boutique organizations, which are nimble and flexible, and well suited to work with startups and emerging companies. Our work with Bioforum is an example of such a model. Sometimes, challenges are inevitable, but they can be overcome with innovative thinking and the right approach to partnership.

2. Developing (and executing on) a clear strategy of which aspects of clinical operations to keep in-house vs. outsource is critical, especially for a smaller-size company. What has contributed to BioLineRx’s success in this area? How do you go about selecting your partners?

Irit: BioLineRx, as much as possible, keeps senior clinical trial management-level roles in house. Our leadership team works with partners as strategic advisors for a range of initiatives and projects, and we also outsource the execution of various activities as needed and when relevant. For us, the outsourcing model that works best is to partner with service providers, who are experts in their fields, rather than using a one-stop-shop model for all our studies. We believe this model contributed to our success conducting our clinical studies. The Motixafortide GENESIS trial is an example of successfully executing together with our partners, who were engaged and invested in our success.

All our partners are carefully selected based on their subject-matter knowledge, execution capability, size, reputation within the industry and recommendations from our peers in the life sciences. When making decisions about which service providers to partner with, we also pay close attention to their ability to communicate effectively and be transparent, as well as their out-of-the-box (creative) thinking. A partner’s problem-solving abilities and, of course, willingness to meet goals and strive for success are crucial factors.

At BioLineRx, we share lessons learned with our team and partners, so that we can make improvements along the way and apply key insights to future studies.

3. When it comes to vendor partnerships, how do you evaluate return on investment (ROI)? What key performance indicators (KPIs) do you monitor to assess performance and the success of a partnership overall?

Irit: KPIs are set by the clinical team in collaboration with various company disciplines for different functions, whether operational, clinical, safety and other.BioLineRx measures the success of the partnership by assessing the predefined KPIs and how issues are addressed when they arise. We place great value on communication, listening and implementing recommendations provided by our partners, and, ultimately, creating a decision-making process that we go through together. We also appreciate partners who are willing to learn and put a lot of effort into mentoring and guiding, as we are equally invested in their success.

4. Sometimes things don’t go as planned and a study needs to be “rescued.” How has BioLineRx overcome such challenges and are there any key learnings from your experience that other emerging companies should keep in mind?

Irit: We had been partnering with a CRO for our Motixafortide GENESIS study and expectations were not met.

After several months of collaboration, we realized that the collaboration doesn’t work for us. Instead, we decided to identify experts who specifically have the right experience for key areas of focus and partner with them. Changing partners in the middle of a study is a tough decision and it must be made carefully and thoughtfully because of the risks involved. That said, it’s important not to compromise on each study’s execution. Always set expectations clearly and openly, monitor KPIs, be transparent, willing to learn and adapt when necessary.

My recommendation to other companies is to be clear on what your KPIs are from the very start and develop an oversight plan for each group or department working on the study, whether they are external or internal. This plan will help you ensure you are effectively monitoring KPIs and the team’s performance, and, as such, give you visibility into whether the study is on track or where it might be lagging. Furthermore, a risk analysis meeting at predefined timepoints and milestones is helpful as part of the KPI monitoring process.

If you find yourself in a situation where mitigation plans are not working, as the study sponsor you should start thinking about what else can be done. At the same time, be cautious not to jump into a “rescue status” all at once. If you get to a point where you believe you have tried everything you can and the risk around delivery/execution or quality of data/process remains high, then it’s time to think of transitioning to another service provider, which must be done with great care so as not to disrupt ongoing operational activities and create further challenges and delays.

5. BioLineRx has much to be proud of and there have been many significant milestones in your journey so far, including the results of the GENESIS study. What do you think contributed to the successful design, conduct and analysis of the study, and what advice would you give to startups in the space based on your experience?

Irit: Of course, a close relationship with our partners was key to achieving study delivery, but we also believe that the relationship with the investigational team is a high priority. It is very important to listen to them and encourage them to share their thoughts, both positive and negative. The BioLineRx team had a good relationship with the investigators and even made changes to the protocol based on the feedback received from them. Another addition to success was ensuring that the key opinion leaders (KOL’s) were very involved in making sure that the protocol was aligned even to CRF form level. Their opinions are significant and provide pivotal insights.