Request for proposal RFP - 026510 - IDENTIFICATION AND VERIFICATION OF PREDICTIVE BIOMARKERS FOR AD-O51.4

In connection with the project „ Clinical trial of the first phase (Ia/Ib) of a fusion protein with a dual anticancer mechanism”, financed from Medical Research Agency (nr. 2022/ABM/05/00006-00)  operating under §8 of the subsidy agreement, Adamed Pharma S.A.  invites you to submit offers for the execution of the below defined subject of the contract.

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

The subject of the contract

The subject of the contract is as follows:

1. Identification of biological factors differentiating the sensitivity of cell lines to the action of the AD-O51.4 molecule based on experimental cytotoxicity data (IC50) for approximately 350 cancer cell lines provided by the Ordering Party, as well as auxiliary data available in external databases (e.g., CCLE, TCGA, etc.), taking into account histological types and molecular subtypes.
2. Identification of potential predictive biomarker(s) for therapy with the AD-O51.4 molecule at the level of available RNAseq data and protein expression measurements, aimed at the possibility of clinical application via IHC staining, ELISA testing, or other available technologies that can be validated and implemented in clinical studies. The analysis should cover both positive markers that identify patients likely to respond to treatment, and/or negative markers that indicate patients unlikely to benefit from therapy.
3. Identification of potential biomarkers differentiating the response of selected cell lines to treatment with the AD-O51.4 molecule versus rhTRAIL at the level of available RNAseq data and protein expression measurements. Determination of the discriminative power of the markers.
4. Analysis of potential correlations between the absence and presence of driver mutations (i.e. those qualifying patients for targeted therapy), and the response to AD-O51.4, with additional consideration of PD-L1 expression levels in lung cancer cases (all subtypes).
5. Assessment of the predictive potential of selected predictive biomarkers using ROC curve analysis to determine the area under the curve (AUC), calculate specificity, sensitivity, balanced accuracy, negative predictive value (NPV), as well as verification of the statistical significance of the results through simulation-based construction of a null distribution and p-value estimation and/or other statistical methods appropriate for the mathematical models used.
6. Verification of selected predictive biomarkers in tumor tissues/biopsies from patients using external data provided by The Cancer Genome Atlas (TCGA) or others. The aim of the analysis is to assess whether the biomarkers identified through the developed model enable differentiation of tumors in terms of their potential sensitivity to AD-O51.4 in real clinical data.
7. Interim reports upon completion of each task from 1 to 6, allowing evaluation of the implementation status of completed tasks and assessment of the readiness to initiate subsequent activities. Reports delivered in English.
8. Final report in English, covering tasks 1 through 6, containing a detailed description of the analyses performed, raw data, obtained results, and final conclusions. Discussion and consultation of the results. Presentation of the results.
9. Verification of predictive biomarkers based on cytotoxicity data for AD-O51.4 on patient-derived tumor organoids. Cytotoxicity data (IC50) and RNAseq data will be provided by the Ordering Party.
10. Final report for task 9, containing a detailed description of the analyses performed, obtained results, and final conclusions, delivered in English. Discussion and consultation of the results. Presentation of the results.
11. Additional analyses, if justified, supporting the identification and verification of predictive biomarkers for AD-O51.4, carried out to deepen the commissioned tasks after verification of interim or final reports, upon the Ordering Party’s request.

The Ordering Party does not permit the submission of partial tenders, i.e., tenders covering only selected tasks.

The interim report for Task 1 shall be submitted within 4 weeks from the date of mutual execution of the Agreement.

The final report for Tasks 1 to 6 shall be delivered within 6 months from the date of mutual execution of the Agreement.

The final report for Task 9 shall be delivered within 3 months from the receipt of the relevant order for the execution of this task, but no later than by the end of 2026.

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 of 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.
   5. being in such a legal or factual relationship with the contractor that there is a justified doubt as to their impartiality or independence in connection with the procurement procedure.
      In order to meet this condition, the supplier is obliged to send, together with the offer, a signed Statement of the lack of connections (Appendix No. 1 to this RFP).
2. Orders cannot be awarded to:
   1. a Contractor referred to art. 7 sec. 1 indicated in lists specified in Regulation no 765/2006 and Regulation no 269/2014 or entered in list on basis of a decision on entry in the list deciding on application of measure referred to article 1 point 3 of the Act of April 13, 2022 on special solutions in field of counteracting supporting aggression against Ukraine (Polish Journal of Laws no 835).
   2. a Contractor whose beneficial owner within meaning of the Act of 1 March 2018 on counteracting money laundering and financing terrorism (Polish Journal of Laws no 593 and 655) is a person indicated in lists specified in Regulation 765/2006 and the Regulation 269/2014 or entered on  list or being such a beneficial owner from February 24, 2022, provided that it was entered on list on the basis of a decision on entry in the list determining application of measure referred to in art. 1 point 3 of the Act of April 13, 2022 on special solutions in field of counteracting supporting aggression against Ukraine (Polish Journal of Laws no 835);
   3. a Contractor whose parent undertaking or subsidiary entity within the meaning of Art. 3 sec. 1 point 37 and 39 of the Accounting Act of 29 September 1994 (Polish Journal of Laws no 217, 2105 and 2106) is an entity indicated in the lists specified in Regulation 765/2006 and Regulation 269/2014 or entered on the list or being such a parent undertaking from February 24, 2022, provided that it was entered on list on the basis of a decision on entry in list determining application of measure referred to in art. 1 point 3 of the Act of April 13, 2022 on special solutions in field of counteracting supporting aggression against Ukraine (Polish Journal of Laws no 835).
      In order to fulfill this condition a Tenderer is obliged to send with the offer signed statement (Appendix No. 2 to this RFP).  

3. This offer is addressed to entities with proven experience in providing similar services. The required experience shall be demonstrated by submitting a declaration of compliance with the requirements specified below, constituting Appendix No. 3 to this Request for Proposal.

   1. At least 3 years of experience in performing statistical analyses aimed at identifying potential clinical biomarkers for oncological therapies.

      The Ordering Party reserves the right to request the Bidder to submit additional documents and explanations confirming the information provided in the declaration (Appendix No. 3).

Proposal preparation  

1. Each correspondence should include the number of the procedure in the subject line: RFP 026510 - IDENTIFICATION AND VERIFICATION OF PREDICTIVE BIOMARKERS FOR AD-O51.4 - Company name / Name
2. Deadline for submitting offer is 26.05.2025 at 23:59. The date may change, about which all Suppliers will be informed.
3. Questions should be submitted via e-mail: sabina.jelen-krzyzaniak@adamed.com, using the sheet Appendix no. 5. The Ordering Party reserves the right not to provide a response in the event that the question(s) are submitted within two days prior to the end of the tender procedure. In order to ensure equal access to information to all Tenderers participating in the procedure, questions and answers (concealing the author of the questions) will be sent to all Tenderers and published on the Ordering Party’s website.
4. The offer should contain at least the following information: Company name, address, VAT/registry number, number of the inquiry, net price, currency, payment terms (in days) and required appendices.
5. If prices in offer are expressed in a currency other than PLN, will be converted using the average exchange rate of the National Bank of Poland as of the date of publication of the tender. If the table of average NBP exchange rates is not published on the date of publication the exchange rate from the last table of average exchange rates published before the date of publication of the contract notice will be used.
6. The cost estimate should be prepared in a spreadsheet file, attached as Appendix no. 4 to this request for proposal: Appendix_4_RFP_026510_Cost proposal. In addition, the Bidder may prepare the bid in its own format. Bids without a completed Attachment No. 4 will not be considered.
7. All required annexes, declarations, and documents must be attached to the offer. The Ordering Party also includes with the request a completed and signed checklist (Appendix No. 6), which will serve to confirm whether all required documents have been submitted.
8. The offer with all appendices can be placed on Adamed Procurement Platform SAP Ariba Network at https://supplier.ariba.com or sent via e-mail to: aleksandra.stojak@adamed.com.
9. Each Tenderer may submit only one offer
10. The Ordering Party does not allow partial offers
11. The Proposal should be prepared in Polish or English
12. Tenders submitted after the deadline will not be considered.
13. The Supplier before time-limit for receipt of tenders is entitled to:
    1. Withdraw the offer by submitting a written notification in the manner describes for submitting offers,
    2. Change the offer – notification of the changes must be submitted by the same rules as the submitted offer, appropriately marked with the note “CHANGING THE OFFER”.

Selection criteria and method of evaluation of submitted offers

1. The Ordering Party has the right to reject an offer submitted by a Supplier that does not meet the conditions for participation in the procedure or if the offer is incomplete or inconsistent with this inquiry. 

2. Criteria for selecting offers:

   1. Net price presented as the cost of performing individual parts of the service package (criterion weight - 100% of the overall score), including all costs of the service provided

3. The Ordering Party shall evaluate offers based on the results of accumulated number of points calculated on the basis of above criteria and scores

4. Criteria	Weight [%]	Assessment method according to the formula
   Net price	100%	net price of the lowest offer / net price of the examined offer x 100 x 100% = number of points Refers to the sum of the component items indicated in the Cost Estimate

5. The Ordering Party reserves the right to negotiate proposals with all the Bidders. Negotiations may have several consecutiveroundswith thepossibilitytoinvitethe Bidderstosubmitthe updated quotation after each round of negotiations.

6. The offer with the highest final number of points will be considered the most advantageous.

7. The results of mathematical operations performed when evaluating the bids are rounded to two decimal places. In the event that at least two offers receive the same score, the decisive criterion shall be the net price for the performance of the required services. 

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

Additional information about participation in the tender

1. Tender is available via the Adamed Group Purchasing Platform at: https://supplier.ariba.com and on website https://www.adamed.com/en/development-and-innovation/requests-for-proposals-and-tenders.
2. Username and password to log in to the Purchasing Platform will be sent to the Suppliers by the Operator by e-mail during registration.
3. Technical requirements. In order to work seamlessly with purchasing platform https://supplier.ariba.com. The user should have at least the following technical capabilities:
   1. PC or Mac with a 1GHz processor or faster and a minimum of 512 MB RAM,
   2. permanent access to the Internet with a guaranteed bandwidth of not less than 1Mb / s,
   3. Internet browser in the latest version. IE 9.0+ or Mozilla Firefox or Chrome 24+ 26 + or Safari 5+,
4. The tender procedure may be repeated only in case of inability to be carried out by the Operator or the Employer. Technical problems on the side of Suppliers will have no impact on the course of the tenders.
5. Prior to the tender procedure, it is advisable to familiarize yourself with the operating instructions of the Purchase Platform attached to the tender.
6. The start and finish dates and configuration of each stage of the tender will be presented on the Purchase Platform and may change, all interested Suppliers will be notified by the system by e-mail.
7. Technical support during the procedure. During the procedure, the Suppliers can obtain technical support at: +48 539 737 818 or in the Platform in the Help tab.

General provisions

1. The contracting authority reserves the right to cancel the procedure without giving any reason at any stage of the procedure.
2. 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.
3. By submitting an offer, you accept all terms and conditions of the procedure without any reservations.
4. 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.
5. 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.
6. If the offer does not contain all the required elements, the Ordering Party may, in justified cases, call the Contractor to supplement it.
7. 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.
8. The Bidder's withdrawal from the conclusion of the contract upon notification of the contractor about the selection of their offer may serve as a basis for the Ordering Party's claims, including those related to the damages incurred (such as delays resulting from the necessity to choose another contractor). In such cases, the provisions of the Civil Code shall apply accordingly. Therefore, the Ordering Party requests that thoughtful offers be submitted, in compliance with all the expected conditions of the order, taking into account the indicated foreseeable deadlines for its execution.
9. It is possible to place additional orders exclusively to the selected Bidder, if they align with the main objective of this agreement, with a value not exceeding 50% of the value of this order
10. The Ordering party will sign a contract with the selected Contractor.
11. The Ordering Party 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. justified and required changes in the project documentation that were impossible to predict at the time of contract execution
    2. the necessity or technical and economic justification for the use of equivalent materials and equipment
    3. the necessity to implement equivalent solutions resulting from technological or operational conditions
    4. financial limitations of Ordering Party resulting in limiting the scope of contracted activities
    5. in the event of an unforeseen necessity, not anticipated at the tender stage, to carry out additional analyses or to deepen the scope of analyses due to their scientific nature and the resulting complexity that is difficult to predict, the Parties allow for the possibility of extending the execution deadline. Any extension of the deadline requires prior written approval from the Sponsor.

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.

Cooperation and communication in the course of preparing responses 

1. All questions related to the subject of this inquiry may be directed via the Adamed Group Purchasing Platform at: https://supplier.ariba.com or via email to: sabina.jelen-krzyzaniak@adamed.com, using an Excel file - Appendix No 5.
2. The list of required documents is available in Appendix No. 6
3. The person authorized to contact the Suppliers on Monday-Friday from 09:00 am to 05:00 pm is Aleksandra Stojak: [aleksandra.stojak@adamed.com].

Appendix No 1  (download)

Appendix No 2  (download)

Appendix No 3  (download)

Appendix No 4  (download)

Appendix No 5  (download)

Appendix No 6  (download)

Creating an offer on the Portal SAP Ariba Network (download)

SAP Ariba Network registration (download)