Compassionate use policy
Dicerna Pharmaceuticals, Inc.

1. Dicerna’s Mission

   1. Our mission is to discover and develop potent, selective and safe RNAi therapies to treat diseases including cardiometabolic, viral, chronic liver and complement-mediated diseases, as well as neurodegenerative diseases and pain.
   2. We conduct clinical research with the goal of obtaining regulatory approval of our products so that we can make them available to patients who need them.

2. Commitment to Patient Communities

   1. We are committed to working collaboratively with the communities we aim to serve.
   2. We support the needs of patients, families, and patient advocates by providing disease education materials, resources for connecting with patient communities and support groups, and updates on current development programs.

3. Clinical Trials Overview/Information

   1. There are three stages in the discovery and development process: discovery, development and delivery.
      
      1. In the discovery stage, the company identifies a potential medicine (or drug candidate) for a specific disease.
      2. In the development phase, the company conducts research and tests the potential therapy, evaluating the drug candidate through clinical trials in humans. Once the company begins testing the drug candidate in clinical trials, it is considered an investigational therapy.
      3. Finally, in the delivery phase, the company works with regulatory agencies to seek approval and make the drug available to all patients who need it. This is based on a review of its benefits, potential risks and needs within the patient community. Once the drug receives regulatory approval in a country, physicians are able to prescribe it to patients.
   2. Information about an investigational therapy’s efficacy and safety is generally limited at the stage in which patients seek expanded access or compassionate use. Studies relating to the investigation therapies toxicity and early studies on how the body handles it will have been completed. However, until the company completes clinical trials in the larger patient population, uncertainties about the investigational therapy’s efficacy and safety profile remain. These uncertainties mean that making investigational therapies available for compassionate use, the company must make very careful assessments.

4. Purpose of the Policy

   1. For now, this policy only applies to Dicerna’s lead compound, nedosiran (DCR-PHXC), for the treatment of PH, which is the company’s only product candidate that may become sufficiently advanced to consider requests for compassionate use.
   2. In general, Dicerna believes that participating in clinical trials is the best way for patients to access investigational therapies prior to approval. The completion of these rigorous scientific studies is a critical step to securing the regulatory approval needed to provide access to treatment for the greatest number of patients with a specific disease.
   3. In some extreme circumstances when participating in clinical trials is not possible, patients with life-threatening diseases or conditions may seek special access to investigational therapies outside of a clinical trial setting. These situations are typically referred to as compassionate use, but can also be known as expanded access, early access, pre-approval access, and emergency use.

5. Compassionate Use Criteria/Considerations (Eligibility)

   1. We also recognize that not all patients may be eligible or able to enroll in a clinical trial. For this reason, we support access to investigational therapies for people with life-threatening disease who meet specific requirements.
   2. At Dicerna, a single request for compassionate use of an investigational therapy may only be considered if all of the following conditions are met:
      
      1. The disease or condition being studied is life-threatening.
      2. There are no comparable or satisfactory alternative therapies or clinical trials available.
      3. Sufficient preliminary efficacy and safety data exist for the investigational therapy and/or investigational therapy delivery device in order for Dicerna to make a benefit-risk analysis consistent with the establishment of a compassionate use program.
      4. Sufficient clinical data are available to identify an appropriate dose.
      5. A patient’s treating physician and Dicerna’s chief medical officer both believe there is potential for the patient under consideration to benefit from the investigational therapy, and there is robust evidence to support this possibility.
      6. Patients who have experienced exceptional safety risks outside of a clinical trial due to another medical condition, which have not been studied to better understand any potential problems.
      7. There are adequate supplies of the investigational therapy to support both ongoing clinical trials and the approved compassionate use.
      8. The patient is not eligible for or a candidate in one of the Dicerna-sponsored clinical trials. Geographic limitations would typically not apply to ineligibility status.
      9. Compassionate access will not negatively impact the clinical development program, in particular, any pivotal clinical trial required for regulatory approval.
      10. The patient’s treating physician makes the request, without Dicerna’s or any other individual’s or organization’s solicitation. This request will provide evidence that the patient will have continual access to the level of medical supervision needed to safeguard him or her while he or she is exposed to an investigational therapy.
      11. There is a regulatory mechanism in the country or region that allows for such compassionate access.
   3. The above criteria are those that Dicerna will consider in determining whether to offer compassionate use; however, Dicerna cannot make a guarantee that a compassionate use program will be available, and, even if a compassionate use program is offered, Dicerna cannot make a guarantee that the investigational therapy will be available to a particular patient.
   4. Dicerna is committed to a fair and impartial evaluation of each request for access to its investigational therapies. All decisions are based solely on clinical circumstances and are guided by the principles outlined above.

6. Procedures for Making Compassionate Use Requests

   1. If all the conditions listed in 5(b) are met, Dicerna will consider compassionate use requests from treating physicians consistent with all applicable local and national laws and regulations. Any pre-approval access to an investigational therapy must at all times comply with the applicable country- and state-specific laws and regulations, including information privacy and medicine importation requirements. Approvals from applicable regulatory bodies and by an Institutional Review Board or Ethics Committee from the treating hospital must be secured.
   2. If approved, the patient (or his or her guardian, if applicable) must provide informed consent and consent to comply with the safety and monitoring requirements defined by Dicerna. The treating physician must also agree to comply with safety and monitoring requirements.
   3. Compassionate use will cease to be made available if, as a result of clinical trials, the investigational therapy does not demonstrate a positive risk/benefit to patients or leads to considerable risk of injury to a requesting patient.
   4. For patients that meet Dicerna’s criteria, treating physicians can make a request via compassionateuse@dicerna.com. All requests must include the treating physician’s name, contact information, professional designations or qualifications, a medical rationale for the request and supporting medical documentation, including an explanation of why alternative therapy cannot be used.
   5. Medical professionals at Dicerna who are familiar with the data collected on the investigational therapy evaluate the request and respond based on the scientific evidence available to the company at the time of the request. Dicerna commits to respond to compassionate access requests within no more than five business days of receipt of the formal request and supporting medical documentation.
   6. More information about Dicerna’s clinical trials is available at www.clinicaltrials.gov. Patients or physicians can also search clinicaltrials.gov for expanded access records by disease and investigator name.
   7. Dicerna will fulfill all regulatory requirements to post details of compassionate use activities on various independent registers, including ClinicalTrials.gov and the European Medicines Agency Compassionate Use website.
   8. Any question about this policy can be directed to the same email address above.