Request for proposal RFP 022594 – SELECTION OF CLINICAL SITE FOR PHASE 1A/1B CLINICAL TRIAL

In connection with a grant application for a Project aiming at clinical development of recombinant fusion protein in targeted anti-cancer therapy in Medical Research Agency program entitled “Development of targeted or personalized medicine basing on cell therapies or protein products”  ABM/2022/5 (Program), Adamed Pharma S.A. invites you to submit offers for the execution of the below defined subject of the contract.

The order will be awarded on the condition of receiving funding from the Project in the above-mentioned Program.

I. Object of the contract:

Conducting phase 1 clinical trial including evaluation of safety, pharmacokinetics and preliminary clinical efficacy of an innovative biomolecule – fusion protein for cancer therapy. The trial should include dose escalation in 3+3 scheme and dose expansion/confirmation with preliminary efficacy assessment in 3 – 4 selected oncological indications.

Study Sponsor (Contracting Authority): Adamed Pharma S.A.

The Ordering Party reserves that disclosure of full information regarding the subject of the contract will take place after signing conclusion of a confidentiality declaration, constituting an attachment to this request for proposals (Appendix No. 1). Contractors with whom a confidentiality agreement has already been concluded should provide it to full disclosure of this request for proposals can be available to them.

The ordered service consists of the following elements:

The offer should include activities related to conducting clinical trial. One contractor will be selected in this RFP. The number of patients to be recruited for the study was indicated in Appendix 2.

1. Conducting of clinical trial phase 1a and 1b.
   1. Goal of the study:
      • Evaluation of clinical safety and tolerability of increasing doses of investigational medicinal product in 3+3 scheme, in patients with solid tumors.
      • Evaluation of pharmacokinetics of investigational medicinal product
      • Preliminary evaluation of efficacy of the investigational medicinal product in patients
      • Recomendation of the dose to be used in phase II clinical trial, treatment regimen and therapeutic indication for phase II study based on results obtained in phase I.
   2. Phase Ia
      An open-label, First-in-Human safety trial of AD-O51.4 in a mixed population of patients with advanced malignancies. Dose escalation according to 3+3 scheme in patients over 18 years old, ho have progressed on standard therapy.
      Phase 1b
      Open-label 4-arm clinical trial aiming at dose confirmation, expansion and preliminary efficacy evaluation in patients of 18 years or older with solid tumors who had progressed on standard therapy.
   3. Investigational medicinal product:
      • Fusion protein with anti-cancer properties.
2. Procedures that will be required in the study, and the timeline for their conductionwere proposed by the Sponsor in the Study Synopsis, that was attached to this RFP (Appendix 2 – confidential). The assumptions proposed in the Synopsis may be slightly modified during the Study Protocol preparation, during consultation with clinical experts, or in the light of new data acquired in the Project.
3. The numberof patients in the study was proposed by the Sponsor in the Synopsis (Appendix 2). The numbers proposed in the Synopsis may be slightly modified during the Study Protocol preparation, during consultation with clinical experts, or in the light of new data acquired in the Project.
4. The study should be conducted and documented according to Good Clinical Practice and relevant guidelines ofInternational Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, Declaration of Helsinki and relevant laws of European Union, local laws, and according to clinical trial documentation prepared by the Sponsor
5. The contract for conducting of the clinical trial will be signed according to the offer presented in the answer to this RFP. The Clinical Sitehas to grant the Sponsor a permission to conduct an audit by the Sponsor or by their Behalf.

II. Timeline for the contracted activities:

1. The proposed offer has to include all assumptions mentioned below, what needs to be confirmed by a statement signed by the Oferent (Appendix 4).

   1. Availability of the documents required by Ethical Committeeand relevant Offices (CV, GCP certificate of thePrincipal Investigator, not older than 2 years) no later than 30 days after contract execution.

   2. Availability of the documents needed to initiate the clinical trial (including certificates of the equipment required for diagnostics of patients, recent resumes of GCP certificates of the Clinical Study Team, executed contracts no later than 30 days after contract execution.

   3. Participation of the study team in site initiation visitand delegation of responsibilities.

   4. Inclusion of the first patient during first 30 days from receiving of the green light for recruitment from the Sponsor.

   5. Inclusion of the last patient in phase Ib before 30.01.2028.

   6. Filling of the electronic Case Report Forms  (eCRF) together with regular answers to queriesno later than 5 days from the last visit/queryuntil the database lock in the study.

   7. Availability of documents required for clinical study closure no later than 60 days from database lock.

2. The Sponsor can modify the timeframe of the study if a relevant regulatory agency/ethical committee does not approve the study described in the offer, or if the Project realization will change independently from the Sponsor.

III. Conditions for participation in the proceedings:

1. The contract may not be awarded to entities related to the Ordering Party personally or by capital. Capital or personal ties are understood as interrelationships between the Ordering Party and the Supplier or persons authorized to incur liabilities on behalf of the Ordering Party or persons performing on behalf of the Ordering Party activities related to the preparation and conduct of the Supplier selection procedure, consisting in particular of:

   1. participating in the company as a partner in a civil partnership or partnership,

   2. owning at least 10% of shares or stocks,

   3. acting as a member of the supervisory or management body, proxy, proxy,

   4. remaining in a marriage, relationship of kinship or affinity in a straight line, kinship of the second degree or affinity in the lateral line or in relation to adoption, care or guardianship.

      In order to meet this condition, the Supplier is obliged to send, together with the offer, a signed Statement on the lack of connections (Appendix 3 to this RFP).

2. The RFP is addressed to entities that:

   1. Declare conduction of the requested study according toGood Clinical Practice and relevant guidelines of International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, Declaration of Helsinki and relevant laws of European Union, local laws,  and according to clinical trial documentation prepared by the Sponsor. The oferent is obliged to deliver relevant statement (Appendix 5).

   2. Declare conduction of the requested study at high quality. To declare this request, the oferer is obliged to deliver signed statement, that the study data will be externally monitored (Appendix 6). Additionally, the Siteshould present the list of past audits/inspections (if applicable).

   3. Have ability to recruit patients who have progressed on all available standard oncological therapies, who declare informed consent for participation in the study with innovative biomolecule administered intravenously and who meet the inclusion and exclusion criteria described in the Appendix 2. (Appendix 7)

   4. Have at least 3 years of experience in early phase clinical trials, what should bedocumented in relevant statement (Appendix 8).

   5. Hire experienced personnel with a know-how to conduct the study:

      • Principal Investigator specialised in clinical oncology who has experience in early phase trials in patients. The experience of Principal Investigator should be documented in recent CV (at least 5 years of experience in clinical oncology)
      • Principal Investigator and the Study Team has to present recent GCP certificate and CV (Appendix 9).
   6. Have abilityto perform procedures described in the Synopsis (Appendix 2). To confirm this, the Oferer should deliver: basic information of the Site (anticipated number of patients with solid tumors in one month during recruitment period, list of personnel with described qualifications, list of equipment required for procedures, including ECG, computer tomograph, access to genetics laboratories of genetics, pathomorphology and radiology for processing and storage of patient’s biopsies. The site should have access to freezer and refrigerator and centrifuge with temperature monitoring and alarm needed for processing and storage of patient’s specimens. This should be confirmed by relevant statement (Appendix 10).

   7. Declare acces to Intensive Care Unit for patients participating in the study, what should be confirmed in the relevant statement (Appendix 11).

   8. Declare access to a hospital pharmacy, where the investigational medicinal product will be stored in the freezer with limited access, temperature monitoring and alarm system. Moreover, the oferer should have access to cytostatic laboratory. This has to be confirmed by relevant statement (Appendix 12).
      Have established cooperation with analytical laboratory where therequired analyses of the samples from the study can be performed, what should be confirmed in the relevant statement (Appendix 13). 

3. The Supplier may use services of subcontractors to perform all or part of services presented in this request for proposals. Supplier is obliged to conclude appropriate agreements with subcontractors.

4. It is allowed to award selected Tenderer supplementary contracts that are consistent with the subject of contract, in the amount not exceeding 50% of the value of this contract.

IV. Proposal preparation:

1. Each correspondence should include the number of the procedure in the subject line: RFP 022594 - PHASE 1a / 1b CLINICAL TRIAL - Name of the center
2. Deadline for submitting offer is 06.09.2022 time. 23:59. The date may change, about which all Suppliers will be informed.
3. Questions can be sent by e-mail: aleksandra.stojak (at) adamed.com, in the form of a completed Appendix 14.
   The Contracting Authority reserves the right not to provide an answer if the question / questions are submitted within two days before the end of the procedure.
   In order to ensure equal access to information to all Suppliers participating in the procedure, questions and answers (concealing the author of the questions) will be sent to all Suppliers.
4. The offer should contain the following information: name and address of the Supplier, number of the inquiry number, net price (EUR or PLN) and payment terms, scope of activity.
5. The offer should be prepared in an oferer’s format (Appendix 15) that should contain cost of  performance of the procedures in the study described in Appendix 2 for 1 patient
   Proposals without a completed Appendix No. 15 will not be considered. Additionally, the Supplier may present an offer on its template.
6. All required attachments, statements and documents should be attached to proposal - Supplier also attaches to the inquiry a completed and signed checklist (Appendix 16), which will confirm whether all required documents have been delivered.
7. The proposal with the required Attachments should be submitted by e-mail to the following address: aleksandra.stojak (at) adamed.com.
8. Each Tenderer may submit only one offer.
9. Contracting Authority does not allow partial proposals.Supplier should ensureperformance of all required services and efficent organization and implementation of clinical trial.
10. Proposal should be prepared in Polish or English.
11. Prices in the offer should be net prices in PLN (PLN) or euro (EUR).
12. If the prices in the offer are expressed in EUR, they will be converted using the 4.4536 PLN / EUR  exchange rate, in accordance with the Notice of the President of the Public Procurement Office of December 3, 2021 on the current EU thresholds, their equivalent in PLN, the zloty equivalent of amounts expressed in euro and the average exchange rate of the zloty in relation to the euro constituting the basis for converting the value of public contracts or contests.
13.  In the case of other currencies, the average NBP exchange rate on the date of the inquiry announcement will be adopted
14. Offers submitted after the deadline will not be taken into account.
15. The Supplier, before the deadline for submitting proposals, has the right to:
    1. withdraw the offer by submitting a written notification in the same way which is described for the submission of offers,
    2. change the offer - notification about the introduction of changes must be submitted according to the same rules as the offer submitted, appropriately marked with the annotation "CHANGE OF THE OFFER".

V. Selection criteria and evaluation methods of submitted bids:

1. The Ordering Party has the right to reject the an offer submitted by a Supplier which does not meet the conditions for

   participation in the procedure or if the offer is incomplete or inconsistent with this inquiry.

   1. Formal compliance with the requirements of the inquiry (point III. 2).

2. Possibility of providing the service within the time frame specified in point II.

3. Criteria for selecting offers:

   1. Net price of the service (criterion weight - 70% of the overall score) for the performance of the procedures in the study described in Appendix 2 for 1 patient

   2. Number of patients declared at the time of recruitment 6 months (weight of the criterion - 30% of the overall assessment) declared in Appendix no 17.

4. The contracting authority will evaluate the offers based on the result of the number of points, calculated on the basis of the above-mentioned criteria and scoring:

   Criteria	Libra [%]	Assessment method according to the formula
   Net price of the servise	70%	net price of the lowest offer / net price of the examined offer x 100 x 70% = number of points
   Declared number of patients	30%	highest number of patients declared / number of patients required to complete the study x 100 x 30% = number of points

5. The offer with the highest final number of points will be considered the most advantageous.
6. The results of mathematical operations performed when evaluating the tender examination are rounded off to two decimal places. 

VI. Selection of the Contractor and manner of announcement:

1. The Ordering Party will select the most advantageous offer on the basis of the offer evaluation criteria specified in this inquiry (point V).

2. The Ordering Party will inform about the results of this inquiry on the Ordering Party's website https://www.adamed.com/en/development-and-innovation/requests-for-proposals-and-tenders and will send them to each Supplier who has submitted his offer.

VII. General provisions

1. The contracting authority reserves the right to cancel the procedure at any stage without giving any reason at any stage of the procedure.
2. The contract will be awarded on condition of receiving funding for the Project in the competition: "Development of targeted or personalized medicine based on cell therapy or protein products" ABM / 2022/5.
3. In the event of cancellation of the procurement procedure, the contractors shall not be entitled to claim reimbursement of the costs of participation in the procedure.
4. By submitting an offer, you accept all terms and conditions of the procedure without any reservations.
5. Withdrawal by the Ordering Party from concluding the contract in the event of notifying the contractor about the selection of its offer, it may not be the basis for claims for the costs of participation in the procedure.
6. In the course of assessing the submitted applications, the Ordering Party may request the contractors to provide explanations regarding the content of the documents submitted by them.
7. If the offer does not contain all the required elements, the Ordering Party may, in justified cases, call the Contractor to supplement it.
8. The contracting authority reserves the right to record sound during technical meetings with suppliers. Sending the offer will be treated as giving consent to record the meetings.

9. The Ordering Party allows the contract terms to be negotiated with the Contractor to a limited extent.

10. The Ordering Party reserves the right to negotiate offers with each Tenderer. Negotiations may have several consecutive rounds with the option of inviting the tenderer to submit an updated bid after each round of negotiations.

11. The contracting authority reserves the right to audit the tenderer prior to signing the contract. In the event of unsatisfactory audit results, the Ordering Party may withdraw from signing the contract. The unsatisfactory results of the audit will primarily include the statement that the conditions specified in point III.2 are not met

    1. The Sponsor can modify the scope and timeframe of the study if a relevant regulatory agency/ethical committee does not approve the study described in the offer, or if the Project realization will change independently from the Sponsor. Expert’s recommendations resulting from consulting of the Study Protocol.

    2. Sponsor can change the study timeline if the recruitment does not meet the statistically relevant values or financial limitations of the Sponsor resulting in the scope limitation.

12. Justified or required changes of timelines and conditions resulting in the unforeseeable(at the time of the offer) conditions. Changing the terms of the order:

    The contracting authority provides for the possibility of introducing significant changes to the contract concluded as a result of the conducted contract award procedure in relation to the content of the offer, on the basis of which the contractor was selected, in the event of the necessity to change the scope of service indicated in the offer / agreed scope, resulting from:

    1. The Sponsor may change time frame for the implementation of  research, as specified in request for proposals, if the relevant authority and / or the relevant ethics committee do not issue a consent and / or a positive opinion for the conduct of this clinical trial.

    2. Recommendations of experts resulting from consultations with experts and the clinical trial protocol.

    3. The Sponsor may change the time frame for the implementation of the research accepted in the inquiry, if the recruitment for the study does not reach the statistically assumed value of the financial limitations on the part of the Ordering Party, resulting in the necessity to limit the scope of works included in the offer.

    4. Necessary or justified changes to the date and terms of delivery of the subject of the contract resulting from unforeseeable reasons.

       Any changes and additions to the contract concluded with the selected Contractor will be made in the form of written annexes to the contract signed by both parties.

VIII. Additional information

1. All questions related to the subject of this inquiry may or be directed to the following e-mail address: aleksandra.stojak (at) adamed.com.

2. The list of required documents is available in Appendix No. 16.

3. The person authorized to contact the Suppliers on Monday-Friday from 08:00 am to 04:00 pm is: Aleksandra Stojak [aleksandra.stojak [at] adamed.com].

Appendix No 1  (download)

Appendix No 3  (download)

Appendix No 14  (download)

Appendix No 16  (download)

Appendix No 17  (download)