DKFZ Drug Discovery Lab (D3Lab)

The D3lab emerged from the DKFZ-Bayer Immunotherapeutics laboratory that over the past 10 years served as the hub for immuno-oncology (I.O.) drug development in the context of the DKFZ-Bayer Strategic Alliance. During this period, our lab functioned as the interface between our academic colleagues at DKFZ and the various functions at Bayer Pharma, thereby bridging the cultural differences between academia and pharmaceutical industry, often referred to as the valley of death. This resulted in a vibrant pipeline of >30 diverse drug discovery projects aimed at the development of I.O. biologicals and small molecule drugs. For 4 of these projects, our lab was involved in the complete trajectory from target validation, through early and late stage drug development, towards the achievement of INDs (investigational new drug applications).

Since the conclusion of the DKFZ-Bayer Strategic Alliance per mid-2024, our team continues this mission as D3Lab, with the goal of valorizing in-house research findings to a level that supports effective clinical translation. Notably, the latter usually requires funding and infrastructure that is not available in academia, and therefore partnering with pharma or founding of a spin-off biotech venture. A typical problem in academia is that scientists file a patent priority application with the intent to enable clinical translation, but subsequently focus on concluding the publication of their finding, after which they move on to creating their next publishable story. Given the ‘publish or perish’ culture, this is fully understandable. The logical, but unfortunate consequence is that the creation of further value with respect to the IP intellectual property (IP) filing is put on the backburner. Notably, the period of two and a half years following the priority filing offer a critically important time window for validation and consolidation of the invention(s) concerned. Subsequently, the IP filing enters the national phase, in the context of which separate filings in different regions/countries of the world have to be arranged and managed. This is when management and maintenance of patents becomes very expensive.

Bottom line: in an academic environment such as the DKFZ, patenting of research findings is only sustainable when limited to well-consolidated IP filings with a clearly defined market potential. The pursuit of IP noncompliant with these standards is a notoriously lossy practice. To avoid an expanding patent portfolio lacking payoff potential, the Go/No-Go requirement for each priority application must therefore involve a well-defined plan towards validation and consolidation of the IP concerned. A main hurdle in implementing this, is the fact that academic scientists are not familiar with critical path research, the rules of which are very different from regular preclinical experimentation. This is where our D3Lab-team, based on hands-on experience, can advise and make concrete experimental contributions. Notably, the scope of the lab has been extended to oncology drug discovery, the rationale being that the honeymoon years of I.O. are over. Consequently, the focus of drug discovery has shifted back to mechanisms directly affecting tumor malignancy. Given the experimental and conceptual complexity of I.O. research, especially with respect to in vivo pharmacology, this is not an obstacle for our team.

Nevertheless, the second main hurdle with respect to the implementation of critical path research is more difficult to overcome. Fact is that true incentives for allocating efforts and resources towards this goal are currently lacking, both for individual scientist and for academic institutes. In spite of all good intentions to improve patient care, the primary criterion for valuing research output is still the number and impact of academic, peer-reviewed publications.

The decision by the DKFZ Management, after conclusion of the DKFZ-Bayer Alliance, to support continuation of our lab indicates that these matters are currently on the DKFZ agenda. In the context of our new mission, the D3Lab team is currently focusing on three efforts:

• Management of the former DKFZ-Bayer portfolio, currently including 8 projects, in particular by addressing critical issues concerning experimental validation and market value. Go/No-Go decisions will be made by the end of 2025, based on the aforementioned criteria, with respect to continuation of these projects and maintenance of the corresponding IP.

• Engagement with selected DKFZ colleagues on novel drug discovery projects, with a focus on validation of the underlying concepts (thus far, 2 projects were initiated)

• Orchestration of a systematic exchange with the DKFZ Innovation Management Department involving critical evaluation of the existing IP portfolio, as well as establishment of a new workflow to provide guidance to DKFZ scientists with respect to the filing and consolidation of new IP.

IP filings DKFZ-Bayer Alliance with involvement DKFZ-Bayer Immunotherapeutics Lab (2016 – 2024; n = 25) 

Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) blocking antibodies:

Anti-CEACAM6 antibodies and uses thereof

•  DKFZ-Bayer Lab members listed as inventors: Jessica PINKERT, Philip BECKHOVE, Yingzi GE

•  WO2016150899A2

•  2016-03-21 Application filed by Bayer Pharma AG

Pharmaceutical combination of anti-CEACAM6 and either anti-PD-1 or anti-PD-L1 antibodies for the treatment of cancer

•  DKFZ-Bayer Lab members listed as inventors: Rienk OFFRINGA, Hans-Henning BÖHM, Philip BECKHOVE

•  WO2020099230A1

•  2019-11-07 Application filed by Bayer Aktiengesellschaft, Deutsches Krebsforschungszentrum

Pharmaceutical combination of anti CEACAM6 and tim3 antibodies

•  DKFZ-Bayer Lab members listed as inventors: Rienk OFFRINGA, Hans-Henning BÖHM, Philip BECKHOVE

•  WO2020126808A1

•  2019-12-12 Application filed by Bayer Aktiengesellschaft, Deutsches Krebsforschungszentrum

Anti-CEACAM6 antibodies with reduced side effects

• DKFZ-Bayer Lab members listed as inventors: Rafael CARRETERO, Rienk OFFRINGA

• WO2023031366A1

• 2022-09-01 Application filed by Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts

Aryl hydrocarbon receptor (AHR) small molecule inhibitors:

2-heteroaryl-3-oxo-2,3-dihydropyridazine-4-carboxamides for the treatment of cancer

• DKFZ-Bayer Lab members listed as inventors: Christina KOBER, Rafael CARRETERO

• WO2018146010A1

• 2018-02-02 Application filed by Bayer Aktiengesellschaft, Bayer PharmaAktiengesellschaft, Deutsches Krebsforschungszentrum

Sulphur substituted 3-oxo-2,3-dihydropyridazine-4-carboxamides

• DKFZ-Bayer Lab members listed as inventors Christina KOBER, Rafael CARRETERO

• WO2019101642A1

• 2018-11-16 Application filed by Bayer Aktiengesellschaft, Bayer PharmaAktiengesellschaft, Deutsches Krebsforschungszentrum

[1,2,4]triazolo[1,5-c]quinazolin-5-amines

•  DKFZ-Bayer Lab members listed as inventors: Christina KOBER, Daniel BAUMANN

•  WO2021028382A1

•  2020-08-10 Application filed by Bayer Aktiengesellschaft, Bayer PharmaAktiengesellschaft, Deutsches Krebsforschungszentrum

Pyrido[1,2,4]triazolo[1,5-c]pyrimidin-5-amines

• Julien Christina KOBER, Daniel BAUMANN

• WO2022029063A1

• 2021-08-02 Application filed by Bayer Aktiengesellschaft, Bayer PharmaAktiengesellschaft, Deutsches Krebsforschungszentrum

Pyrido[1,2,4]triazolo[1,5-c]pyrimidin-5-amines

• DKFZ-Bayer Lab members listed as inventors:  Christina KOBER, Daniel BAUMANN

• WO2022029063A1

• 2021-08-02 Application filed by Bayer Aktiengesellschaft, Bayer PharmaAktiengesellschaft, Deutsches Krebsforschungszentrum

Mitogen-activated protein kinase kinase kinase kinase 1 (MAP4K1/HPK1) small molecule inhibitors:

Substituted pyrrolopyridine-derivatives as MAP4K1 modulators for the treatment of cancer diseases

• DKFZ-Bayer Lab members listed as inventors: Rafael CARRETERO, Rienk OFFRINGA

• WO2018228923A1

• 2018-06-07 Application filed by Bayer Pharma Aktiengesellschaft, Bayer Aktiengesellschaft, Deutsches Krebsforschungszentrum Heidelberg

Substituted pyrrolopyridine-derivatives

•  DKFZ-Bayer Lab members listed as inventors: Rafael CARRETERO, Rienk OFFRINGA

• WO2018228925A1

• 2018-06-07 Application filed by Bayer Pharma Aktiengesellschaft, Deutsches Krebsforschungszentrum Heidelberg

Substituted pyrrolopyridine-derivatives

• DKFZ-Bayer Lab members listed as inventors: Rafael CARRETERO, Rienk OFFRINGA

• WO2018228920A1

• 2018-06-07 Application filed by Bayer Pharma Aktiengesellschaft, Deutsches Krebsforschungszentrum Heidelberg, Bayer Aktiengesellschaft

Substituted pyrrolopyridine-derivatives

• DKFZ-Bayer Lab members listed as inventors: Rafael CARRETERO, Rienk OFFRINGA

• WO2019016071A1

• 2018-07-12 Application filed by Bayer Pharma Aktiengesellschaft, Bayer Aktiengesellschaft, Deutsches Krebsforschungszentrum

Substituted pyrrolopyridine-derivatives

• DKFZ-Bayer Lab members listed as inventors: Rafael CARRETERO, Rienk OFFRINGA

• WO 2020120257A1

• 2019-12-04 Application filed by Bayer Aktiengesellschaft, Deutsches Krebsforschungszentrum

   

Spiro-fused tricyclic MAP4K1 inhibitors

• DKFZ-Bayer Lab members listed as inventors: Rafael CARRETERO, Rienk OFFRINGA

• WO2021074279A1

• 2020-10-15 Application filed by Bayer Aktiengesellschaft, Deutsches Krebsforschungszentrum

2'-(quinolin-3-yl)-5',6'-dihydrospiro[azetidine-3,4'-pyrrolo[1,2-b]pyrazole]-1-carboxylate derivatives and related compounds as MAP4K1 (HPK1) inhibitors for the treatment of cancer

• DKFZ-Bayer Lab members listed as inventors: Rafael CARRETERO, Rienk OFFRINGA

• WO2021249913A1

• 2021-06-07 Application filed by Bayer Aktiengesellschaft, Deutsches Krebsforschungszentrum

MAP4K1 inhibitors

• DKFZ-Bayer Lab members listed as inventors: Rafael CARRETERO, Rienk OFFRINGA

• WO2022167627A1

• 2022-02-04 Application filed by Bayer Aktiengesellschaft, Deutsches Krebsforschungszentrum

New MAP4K1 Inhibitors

• DKFZ-Bayer Lab members listed as inventors: Rafael CARRETERO, Rienk OFFRINGA

• WO2025021997A1

• 2024-07-26 Application filed by Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts

Diacyglycerol Kinase (DGK) alpha and zeta-selective small moleculeinhibitors:

Substituted aminoquinolones as DGKalpha inhibitors for immune activation

• DKFZ-Bayer Lab members listed as inventors: Christina KOBER, Rienk OFFRINGA

• WO2021105115A1

• 2020-11-24 Application filed by Bayer Aktiengesellschaft, Bayer PharmaAktiengesellschaft, Deutsches Krebsforschungszentrum

Substituted aminoquinolones as DGKalpha inhibitors for immune activation

• DKFZ-Bayer Lab members listed as inventors: Christina KOBER, Rienk OFFRINGA

• WO2021105116A1

• 2020-11-24 Application filed by Bayer Aktiengesellschaft, Bayer PharmaAktiengesellschaft, Deutsches Krebsforschungszentrum

Substituted aminoquinolones as DGKalpha inhibitors for immune activation

• DKFZ-Bayer Lab members listed as inventors: Christina KOBER, Mareike GREES, Rienk OFFRINGA

• WO2021105117A1

• 2020-11-24 Application filed by Bayer Aktiengesellschaft, Bayer PharmaAktiengesellschaft, Deutsches Krebsforschungszentrum2020-06-19 Priority toEP20181065.2

Substituted aminothiazoles as DGKzeta inhibitors for immune activation

• DKFZ-Bayer Lab members listed as inventors: Mareike GREES, Corinna LINK, Rienk OFFRINGA

• WO2021214019A1

• 2021-04-20 Application filed by Bayer Aktiengesellschaft, Deutsches Krebsforschungszentrum

Substituted aminothiazoles as DGKzeta inhibitors for immune activation

• DKFZ-Bayer Lab members listed as inventors: Corinna LINK, Rienk OFFRINGA

• WO2021214020A1

• 2021-04-20 Application filed by Bayer Aktiengesellschaft, Deutsches Krebsforschungszentrum

Combinations of DGK (diacylglycerol kinase) inhibitors

• DKFZ-Bayer Lab members listed as inventors: Catherine OLESCH, Frederik CICHON, Rienk OFFRINGA

• WO2024165470A1

• 2024-02-05 Application filed by Bayer Aktiengesellschaft, Deutsches Krebsforschungszentrum

Combination of CCR8 antibodies with DGK inhibitors in the treatment of cancer

• DKFZ-Bayer Lab members listed as inventors: Rienk OFFRINGA

• WO2024165468A1

• 2024-02-05 Application filed by Bayer Aktiengesellschaft, Deutsches Krebsforschungszentrum