ONO PHARMACEUTICAL CO., LTD.
R&D Presentation Meeting
February 24, 2023

[Number of Speakers]

4
Gyo Sagara
Toichi Takino
Kiyoaki Idemitsu
Yukio Tani

President, Representative Director, and Chief
Executive Officer
Member of the Board of Directors, Senior Executive
Officer, Executive Director of Discovery and Research
Member of the Board of Directors, Executive Officer,
Executive Director of Clinical Development
Corporate Executive Officer, Head of Corporate
Communications

Presentation

Sagara: When we announced our financial results last May, we talked about our investment policy in our fiveyear mid-term plan. Specifically, we will invest JPY600 billion in R&D over the five-year period from FY2022 to
FY2026.
In addition, JPY250 billion in strategic investments will be made to strengthen the drug discovery business,
expand business domains, and the management base. These two are our R&D and related business
investments.
Currently, we have been already making investments to strengthen our drug discovery business, such as
through alliances with research platforms, acquisition of compounds for expansion of our pipeline, especiallythose that can be marketed globally, and investments in venture companies. The investment is proceeding
steadily. I am not going to explain each individual investment in detail, but we are making steady progress on
the strategic investment JPY250 billion.

1Currently, we have started global development with the pipeline, as you can see, focusing on drugs discovered
in-house. In total, we have 10 compounds and 11 clinical trials, and we have one compound with which two
indications have been investigated.
While pursuing unique products moving out from our drug discovery policy for Compound Orient approach,
we will also focus on oncology, immunology, and neurology. We are following a policy of drug discovery thatis to try out any interesting and unique drug that comes our way. As you can see, we have started trials mainlyin the areas of oncology, neurology, and immunology.
We are now working diligently to successfully conduct two or three trials in the future and obtain global
approval, so that we can supplement Opdivo’s cliffs and grow further.

2

Takino: This is a stone monument that describes our corporate philosophy at our main laboratory, the Minase
Research Institute. With the philosophy of Dedicated to the Fight against Disease and Pain, we are dedicatedto delivering innovative new drugs.

3Our approach to R&D has also undergone some transition, as the president mentioned at the beginning of
this presentation, we would like to continue to fight for the patients in areas where many of their medical
needs remain, which are oncology, immunology, and neurology, and to create drugs in these three areas.
However, we do not want to limit our opportunities in those three areas only, but rather, we have designatedspecialty as our fourth priority.

4This slide represents our drug discovery policy that we use in our explanation for external parties, but I think
it is also difficult to understand with this slide only. Therefore, I would like to talk about Ono’s drug discovery
by explaining from a view of open innovation with examples.

5

Open innovation is an extremely important initiative, that it would not be an exaggeration to say that it is alifeline for Ono. We would like to create innovative drugs that other companies cannot do, by actuallyexperimenting with open innovation.

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In fact, if we look back at examples in the last two years, in terms of open innovation, and collaborations withother companies, there are doing more than 10 times as many examples as shown here, but we have omitted
basic joint research with academia and other alliances with CROs, and limited the list to, that have beenreleased to the press.
We are expanding our drug discovery and research collaboration in terms of number of alliances, for example,
in 2021 and 2023, including this week’s collaboration with Cue Biopharma.
As the president mentioned at the beginning of this presentation, we are committed to investing in research,
not only in terms of cost and funding, but also building a structure and system to actually carry out this work.
We will continue to strengthen our own drug discovery activities while looking outside of the Company.

7

This shows the summary by disease area or modality. The point is I can tell you that we’re working on a lot ofdifferent areas. Another thing is that, as you can see on the right-hand side of the page, biologics initiatives
are increasing in Ono.

8

I would like to talk about each of these initiatives. At first, I would like to talk about the seeds of drug discovery
and the exploration for drug target.

9There are incubation labs in the US, one is LabCentral on the east coast, and the other is MBC BioLabs on thewest coast. We have a sponsorship agreement with them and we will continue to provide financial support tostartup ventures that wish to enter their incubation labs, so that we can catch up with new drug discovery
ideas and trends, access them, and link them to future seeds for drug discovery alliances. With that
expectation, we are sponsoring an initiative entitled ONO Golden Ticket.

10We are also participating in the UC Drug Discovery Consortium, UC DDC, at the University of California in the
US. This is a framework for us to explore collaborative research opportunities with UCSF, UC Berkeley, UC
Davis, the UC group with eight life sciences faculty or UC universities that are trying to advance research withnew ideas.

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Also, Knowledge Palette, Inc., which is a domestic venture, has quite outstanding technology in the analysisof large-scale transcriptomes. By partnering with this company, we are now trying to build a foundation in
preparation for the future data-driven drug discovery, from the conventional drug discovery, which is often
expressed in vague terms, such as researchers’ intuition or discernment. We are also trying to establish afoundation that can be used to discover and verify new target molecules and mechanisms of action.

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Apart from establishing these systems and network, PrecisionLife in the UK is looking for new specific seeds
in the area of central nervous system.
Recently, bioinformatics has become very useful, and this company has its own composite analysis platform
as well as its own unique patient data assets available. By partnering with this company, we hope to detectand analyze the genetic background and fluctuations of certain patients with central nervous system diseases
who are resistant or refractory to certain drugs, even if they continue to use them for a long time. By doing
so, we are expecting to discover new drugs, and we have begun to work on this project.

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This is a new theme in oncology and an oncology drug discovery program with KSQ Therapeutics in the US.
This company is a venture company started from a unique drug target discovery technology by a prominent
professor from the Broad Institute.
While they were working to find new targets using CRISPR, which is named CRISPRomics, and they have aninteresting project on the DNA damage response and PARP inhibitors, which I think will lead to synthetic lethal
drugs. we have decided to take over this project.
As described above, we are taking a variety of approaches at different levels to search for the seeds of drug
discovery.

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Next, I would like to talk a little bit about what we are doing as a drug discovery modality when attractive drug
targets emerge from the search for such drug discovery seeds.

15This is our partner’s venture in the field of multi-specific antibodies, which we have been working on for some
time.

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In particular, in our collaboration with Merus, ONO-4685 is currently in the Phase I stage as our clinical project.
TAs expected reactions of the PD-1 and CD3 bispecific antibodies, as shown in the blue box on the left, it
suppresses activated T cell and as shown in the red box on the right, it has a trans-acting or engager like effect,
which means that activated T cells are injured. We are currently developing it for autoimmune diseases andT-cell lymphoma, assuming both of these effects.

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We are not only working on bispecific or multi-specific antibodies. As for ordinary antibodies, I think thetechnology to create antibodies has been dramatically accelerated in the development of the COVID-19
treatment drugs. We are working with Memo Therapeutics to create antibodies against immune-oncology
new targets.

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Our approach to antibody drug discovery is not limited to oncology. We also have been working in the areaof central nervous system with several projects of Neurimmune in Switzerland. In fact, as shown in this slide,
Neurimmune is a venture company, which is expected to have an advantage in the generation of useful
antibodies, by adding a library of B-cell clones from healthy elderly, based on the assumption that healthy
individuals have lived a long and healthy life, while probably overcoming various types of diseases.
Neurimmune's track record includes a project on the Aβ antibody Aduhelm with Biogen, and we are also
working with them on several projects targeting new drug discovery targets for neurodegenerative diseases.

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In the field of autoimmune and inflammatory diseases, we are of course also engaged in antibody researchcollaboration. This is a partnership with academia. We have started a research collaboration with Monash
University, where Dr. Robert is an outstanding professor in the field of GPCR, where there are many cases thatthe antibody creation is not always easya field where antibody creation is not always straightforward.

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This is all about antibodies. Another example of a biologics project is, that we are currently working on analliance with Fate Therapeutics. As you know, we are working on iPSC-derived CAR-T. The level of technology
of CAR-T and gene editing technology is also very high, and we are now in the process of arming CAR-T to its
strongest state by making various modifications that are possible with current science and challenging solid
tumors that have been difficult to be effective so far.
Currently, it takes about one month in preparation in the treatment with autologous CAR-T. The preparation
process has imposed a burden on medical institutions. By using iPS cell-derived products, we expect that it
will be possible to create CAR-T products that can be handled off-the-shelf, similar to the distribution ofordinary pharmaceuticals.
Specifically, as already announced by Fate at last year's ASH meeting, that seven gene-edited, HER2-targeted,
iPSC-derived CAR-T cell product platform, which, of course, avoids host attacks and improves tumor migration
while increasing CAR-T activity so that it does not get fatigued. This is to arm CAR-T as much as possible.

21Ordinally, we disclose the ONO number at the stage of entering the clinical stage, but this time, due tocircumstances with our partner, we have announced the development code of ONO-8250. We expect tomove it to a clinical phase within a year or so.
This is an example of basic data showing that when used in combination with other antibody drugs, theefficacy can be further enhanced in a synergistic manner.
The basic data has shown that ONO-8250 is almost equally effective in killing the cell due to HER2 antibodies.
When used in combination, we have seen exciting data that has been shown to be so effective enough tocause cancer regression.

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As for modalities other than CAR-T, the approach of modifying cytokines to extract only the good parts of
their effects is gaining renewed attention through engineering technology and biological elucidation.
We have also signed an option agreement for CUE-401, which Cue Biopharma is working on, since we areinterested in its potential of dual-specificity fusion protein to both IL-2 and TGF-beta.
This is an approach focusing on regulatory T cells, or Treg. I think it is well known recently that Tregs play arole in tumor immunity by suppressing the immune response to attack cancer in the tumor microenvironment.
In the case of autoimmune diseases, on the other hand, if the regulatory T cells are more active bothquantitatively and qualitatively, the excessive autoimmune response will be suppressed. We are hoping to
induce Tregs efficiently with a wide range of repertoires to treat the inflammatory T cells in autoimmune
diseases that tend to be rich.

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As for cyclic peptide, we are working on as a modality option, in cooperation with PeptiDream Inc.

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We are also working with Captor Therapeutics in Poland to apply this approach to targeted protein
degradation, TPD.
These are the open innovations we are working on regarding drug discovery modalities.

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I have talked about drug discovery seeds and drug discovery modalities. I would like to finish with a little
update on what we are doing in other technologies, such as digital, AI, and robotics.

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As you can see here, we have introduced automated robots in our company for the small-molecule creation
cycle that can be automated. We are also working to make the synthesis cycle as efficient as possible by using
the AI design in the upper left corner to make predictions, and we are refining the technology here byincorporating the AI design of Iktos.

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In addition, with regard to the visualization of target proteins, it is no longer necessary for me to mention thatthe level of electron microscopy has been improved as well as X-ray structural analysis. We are now
conducting joint research with Curreio, Inc. and working to improve these visualization technologies and linkthem to drug discovery.
We may announce this at a later time in the future, but we are planning to use supercomputers to further
accelerate and enhance the process while making full use of the latest AI technology.

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I would like to mention one thing about iPS. iPS is very important not only for direct therapeutic applications,as in the case of CAR-T mentioned earlier, but also as a tool for drug discovery evaluation.
It has been nearly three years since we introduced Mahoro, a humanoid dual-armed robot, and we are steadily
establishing an evaluation system to overcome the difficulty of reproducibility, which is the challenges of using
iPS cell.
Based on this, we are working with various partners in Japan and overseas to create a variety of systems. We
would like to continue to use iPS as a valuable evaluation system that reflects human biology and disease
biology in a robotic form, and we would like to develop it into image analysis.

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In the area of image analysis, we are working with National Institutes for Quantum Science and Technology,
QST. The importance of synuclein as one of the protein aggregations in neurodegenerative diseases is
becoming increasingly clear, and we have finally succeeded in developing PET ligand. I hope that we will beable to link the drug discovery to clinical development in this area of disease in the future.

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We are confident that this kind of open innovation will eventually lead to the creation of unique andinnovative new drugs by actively promoting open innovation, while incorporating seeds and technologies ofdrug discovery, including modalities. I would like to briefly touch on how we have created a system to support
this open innovation itself.

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We have Ono Pharma Foundation, which promotes research grants to top academics in the US, and Ono
Venture Investment, which focuses on start-up ventures. We also have the discovery research alliancedepartment, which promotes research with ventures and discovery in alliances with academia, and thebusiness development department that aims at partnering for the projects on clinical stage. We work on withthese three pillars in this system, and in particular, the business development department and the discovery
research alliance department are committed not only for financial investment but also for human resources,
with a total of about 100 people working in these divisions.
I think it is unusual for a company of our size to be committed to external alliances, and that we are actually
starting to gradually see the output of this commitment.

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As for Ono Venture Investment (OVI), these are our current portfolio. While I will not mention about theportfolio companies, we invest in ventures that excel in a variety of technologies, including fibrosis, electron
microscopy, oncology, gene editing, and AUTAC technology.

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Ono Pharma Foundation in the US has world-renowned scientific advisory board professors on board. We
have one bright and happy news. Among one of them, Dr. Bertozzi of Stanford University was awarded theNobel Prize in Chemistry last year for click synthesis. Looking back on our history, we believe that we havebeen able to work together at such a high level of high science, and we would like to lead to the creation of
new epoch-making drugs. We believe that there is the groundwork to do so.
This is all from me, and I summarized our efforts through open innovation extensively. I think I could explain
how we value open innovation very highly and are striving for drug discovery in a way that is driven by it.
We will continue to take on challenges that other companies cannot, and we will continue to create more andmore materials for our company’s growth.
That is all from me.

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Idemitsu: I would like to introduce Itolizumab.
In addition to our own research, we are also actively engaged in the acquisition of external assets. Itolizumab
is a compound for which we obtained an exclusive option rights from Equillium in the US last December for
development and commercialization in the US and countries around.
It is an antibody product targeting at CD6 and is intended for acute graft-versus-host disease, acute GVHD,
and lupus nephritis. It is a compound that will contribute to the expansion of our pipeline in the immunology
area, one of our priority franchises.

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CD6 is expressed on T cells and involved in adhesion. T cells are activated by attaching to various cells to
produce an immune response. For example, cells adhere to each other by binding CD6 on T cells and ALCAM
expressed on APC, antigen-presenting cells.
T cells become activated, proliferated, and differentiated. Autoimmune disease occurs when activated T cells
cause an abnormal immune response in various organs.

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Itolizumab suppresses abnormal activation, proliferation and differentiation of T cells by inhibiting the bindingof CD6 and ALCAM, thereby controls autoimmune diseases.

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First, I will explain GVHD, one of the target indications. Hematopoietic stem cell transplantation (HSCT) is oneof the treatments for blood cancers such as leukemia. When hematopoietic stem cell transplant is performed,
GVHD is caused when immune cells of the transplanted donor attacks the cells of patient, recipient side.
GVHD develops in less than 50% of transplant patients. According to the literature, depending on the severityof the disease, in patients of Grade 3 and 4, classified into high risk, more than 40% patients will die within six
months. This is a very serious disease.
In addition, in patients of Grade 1 and 2, classified into standard risk, more than 20% patients will die within
six months.
GVHD is a very serious disease. Steroid has been used for the treatment. First, methylprednisolone, an
injectable steroid is administered, followed by oral steroids. By adding Itolizumab to this, we expect additional
effects.

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In Phase I, Itolizumab is administered every two weeks for five doses with steroids. In three dose regimens of
0.4, 0.8, and 1.6 mg/kg, it is evaluated for complete response rate on disappearance of all organ lesions.

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Here are the results. As you can see, the high dose of 1.6 mg produced 60% complete response. Generally,
the response rate for standard therapy, so-called steroid therapy, is 30% to 40%. We consider that theadditional effect was suggested.

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Phase III is currently underway. In Phase III, Itolizumab (n=100) is evaluated versus placebo (n=100) in highrisk patients Grade 3 and 4, as well as Grade 2 having the lesion of lower gastrointestinal tract. The primary
endpoint is complete response rate at day 29.
We will decide whether to exercise the option rights based on the results of this interim analysis.

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Next, I will explain another indication of lupus nephritis. Lupus nephritis is a disease where the development
is very difficult, although the therapeutic agents have recently been approved gradually.
Generally, the combination of steroids and an immunosuppressive agent, Cellcept (mycophenolate mofetil)
is used for the treatment of lupus nephritis. Phase 1 is ongoing with Itolizumab by adding this combination
therapy. The primary endpoint is complete renal response.

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Here are the results of the ongoing Phase I, still in 12 patients. The dark green color is the complete response.
It is still in progress, and the primary evaluation will be conducted at week 28. More than half of the patients
have not yet reached week 28. The UPCR, which is an index in all cases, is downward, indicating that a
response has been obtained in the previous cases, and the complete response has already been observed insome cases. Although it is still immature result, we believe that this suggests a response on the efficacy.
In addition to the GVHD mentioned earlier, we plan to determine option rights by evaluating the top line datafrom this lupus nephritis study.
That concludes my introduction for Itolizumab.

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Question & Answer

Questioner 1: As for Itolizumab that you just explained, can you tell me when you expect the results of GVHD,
lupus nephritis, and LN will be available?
Idemitsu: We have not disclosed a definite time frame, but we do not expect it to take that long.
Questioner 1: Is it correct to imagine that each of them will appear sometime in 2023?
Idemitsu: I believe it will be out by 2024 when we will decide if we will exercise the option.
Questioner 1: I understand. This Itolizumab, I think there was some talk during the last Q3, that if this is thefirst of the US development or Velexbru. I think these two are not overlapping in terms of business andseparate from each other. Is my understanding correct?
Idemitsu: Do you mean timing or franchise?
Questioner 1: I mean the way of sales or commercial platform.
Idemitsu: Both are covered by hematology, so we believe there is a synergistic effect.
Questioner 1: I understand. May I assume that you are still putting in or acquiring from the outside some ofthese products for the launch of Velexbru, targeting about 2025 or 2026? Is that correct?
Idemitsu: We are always willing to actively acquire assets, not limited to this area.
Questioner 1: I understand. Thank you very much. I think there was a modality chart somewhere showing
various projects with various modalities. Looking at that chart, of course, you are doing a lot of biologics.
There is only one peptide in terms of the number of projects. After trying various ways of doing this, do you
think that you are very satisfied with the current form of the alliance, or do you think that it is difficult toincrease the number of peptide project or the priority is declining?
Takino: That is starting as a technique, and we have not yet seen the budding of this technology in any
particular area, so we are keeping it in this form.
I think we will be able to develop the project in the future, perhaps in the form of drug discovery alliances,rather than just general technology licensing. However, the current implication is that we have secured oneof the modalities as a technical license.
Questioner 1: What is the progress so far, as expected or rather faster or slower than expected?
Takino: It’s 50-50. It is also true that this is an area that requires much more know-how than expected. On
the other hand, I believe that the potential of cyclic peptides is high, and I know that some other companies
are actively explaining this to the public.
Questioner 2: At the beginning of the presentation, I think the president mentioned something that you
changed the idea a bit from the “Compound Orient” approach. When I started covering your company, thefirst impressive word I heard was Compound Orient. I wonder whether this method worked or not in the end.
If it worked well, I would like to know a little bit about what came out of it. This is my first question.

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Takino: Looking back at the history so far, I think it is appropriate to describe our attitude of pursuinginteresting compounds as the Compound Orient approach, such as prostaglandins and PD-1.
However, as the time passes, I think it is natural that the drug discovery approach itself evolves as various
biological mechanisms are being elucidated, which could be called translational research. Various
technologies and information such as gene editing and informatics are becoming available.
In today's presentation, I think that various ventures are delving into biology using various proprietary
technologies.
We believe that it is now essential to catch up with those as the importance of the expertise, knowledge, andknow-how of the disease is increasing. We have been conducting research on CNS, along with cancer andimmunology for many years, but have had no drugs for CNS. Therefore, we have decided to raise a sign andwork on these areas as a franchise in these four priority disease areas, while the fourth is all-around.
It is also true that the commitment to the central nervous system has contributed to the acceleration of iPS
research and infrastructure. I believe that we are now entering an era that commitment to the biology side isextremely important. I hope I answered your question.
Questioner 2: In relation to this, I would like to ask you about your company’s concept of a drug discovery
platform, or to put it another way, a technology platform. I think it will be difficult to develop this platform if
it is based on this approach or research approach.
Takino: In general terms, I think that argument will come up. However, I think it is worth mentioning that all
the researchers are consciously working to strengthen the inside by using the outside.
In other words, what kind of things will be created as a result of the inward-looking thinking of inside, I thinksuch an approach is highly questionable in this day and age. We believe that our strengths will ultimately growas a result of our efforts to incorporate a variety of things through trial and error, and if we find a great fit, we
will expand and explore it.
Questioner 2: Finally, about Itolizumab, are they the only indications? If only those, I’m not sure if it is enoughto draw much attention to it. What do you think?
Idemitsu: I think these two indications alone are interesting, but other indications besides them are underinvestigation. We cannot say anything, as the data has not yet been available, but we are conducting or
preparing clinical trials for other diseases as well.
Questioner 2: Is it an inflammatory system?
Idemitsu: It is an autoimmune disease.
Questioner 1: Now that we are talking about other indications of Itolizumab, isn’t this the one that it has been
approved and is marketed for psoriasis in India by Biocon, I believe? Based on that, do you think psoriasis is
not so interesting?
Idemitsu: Biocon, an Indian company, has launched it for psoriasis, as you mentioned. It has an excellent
safety profile and a significant difference in efficacy compared to placebo, but we have not yet decided
whether we will develop it for psoriasis because we need to compare to existing drugs in terms of efficacy.
Questioner 1: If I subtract out everything except psoriasis, with my thin imagination, the only thing left is
UC/CD, which is the most competitive and difficult. Is it the wrong way to look at it?

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Idemitsu: I think it’s not too far off the mark in the sense that there is unmet need. I have to refrain fromstating it here because of the other company. However, in the sense that unmet needs remain, we think thatcolon is one candidate indication.
Questioner 1: There are, of course, other possibilities besides the ones just discussed.
Idemitsu: If T cells are involved in all autoimmune diseases, I think there is a possibility to control them bysuppressing T cell adhesion
Questioner 3: First of all, there were questions about Itolizumab, so I would like to continue with that. I would
like to consider the GVHD potential of this drug and would like to know a few things first.
In terms of this first line treatment of GVHD, you mentioned steroids earlier, but should we only consider
steroids as a competitive agent? Since it is an add-on, I don’t think steroids are basically a contender, but I
would like to know if there are any new drugs that could be a contender in the first-line treatment.
Also, you have given us the number of target patients as 4,500. I think the target patients are between grade
2 and 4, but approximately what percentage of them each?
Also, you said that you will consider options during 2023 in that development plan, so maybe Phase III will befinished during 2023, but I think there is a little bit of time blank between the time and the market launch in
2026. I think it would be possible to get it on the market a little earlier, as I feel that this type of thing would
come with priority review and such, but could you tell me more about that?
Idemitsu: We are thinking of going first for the first-line treatment.
We are not disclosing the timing when the result will be available. We will have the interim result in 2024.
Based on the interim result, we will decide whether or not to exercise the option, and then the trial willcontinue for a little longer.
Of the 4,500 patients in the US, we estimate that the number of patients with grade 3, 4 and grade 2 lower
gastrointestinal disorders, which are currently the target of Phase III, is roughly about half of the total number.
Questioner 3: Secondly, and lastly, I understand your current approach to fundamental technologies andmodalities from the slide on page 10, but could you tell me about your company’s structure for managing
these projects? How does your company respond to each of these companies? For example, I would like toknow if there is a group for small-molecule oncology and if staff of the group is handling this or how yourcompany manages this.
I also think that since you are running so many projects, some of them will be able to enter into clinical trials
more and more as they work out. When it comes to reality, I think that the organization of your company toimplement Phase I will become an issue, or rather, a point that needs to be further strengthened. Could you
please tell us about your current status in that area, the first-in-human clinical trial system? That is all.
Takino: The way we work together in the drug discovery phase varies considerably depending on the project
and the partner. However, if the medicinal chemistry or synthesis part is the main collaboration, for example,
that is where each concerned division will work together directly. Depending on the tasks, the partner may
do all the work, or they may work with us on a 50-50 basis. It varies depending on cases. All projects arecarried out in close cooperation with the respective sites, as I mentioned the medicinal chemistry as an
example.
Questioner 3: Is this being adequately handled on-site? I think you are affiliated with quite a few now.

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Takino: Yes, that’s right. I think it has been working well and will continue to do so.
Idemitsu: Next is regarding Phase I. We have a system in place in Japan to implement Phase I without any
problems, and we also have experience in implementing many Phase I trials even in Europe, so we can do so
without any problems.
In addition, we have recently implemented Phase I in the US, and by further focusing on this, we haveestablished a system that enables us to implement Phase I as quickly as possible in any area without problems.
We have almost established a system where we can conduct Phase I studies in any regions as firmly as possible,
taking into consideration the next phase, and are now in the process of further strengthening the system.
Questioner 3: Then I understood that you have a system in place that can manifest in the number of pieces
that you have given us on the 10th slide.
Questioner 4: Let me confirm about Itolizumab, although it overlaps a little bit with what you mentioned
earlier. In the Phase III EQUATOR study, the primary completion date is December 2023 according to theclinical trials. Does it mean an interim analysis? Also, I believe you have got first track and orphan drug
designations. Can you tell me if the application is possible depending on the results of the interim analysis, ordoes the interim mean that the decision is only for the futility?
Idemitsu: The details are confidential, so I am sorry I cannot disclose. However, the interim analysis for ourjudgement is the result from 100 cases. After that, we will basically apply for approval after obtaining the final
results after conducting the study in the rest of 100 cases.
Questioner 4: By the way, do you have any information about the current recruiting state?
Idemitsu: We have just started, so it is a bit difficult to say.
Questioner 4: Looking at Equillium’s slides, there are about three different dates for the exercise of option
rights. Will you make a decision based on the top line of lupus nephritis and the interim analysis of the
EQUATOR trial?
Idemitsu: We plan to make a decision on both together.
Questioner 5: First of all, you introduced the various modalities that your company is currently working on.
In the field of oncology, in my opinion, the most exciting things in the field of oncology are the undruggabletarget and cold to hot. In short, you would like to make PD-1 work more effective in patients in whom PD-1 isineffective. These two things are still very exciting for us as a person involved in the market.
Looking at the current list of modalities, I see that undruggable is probably the case with Captor Therapeutics.
I think that attaching to something that is difficult to attach in the first place, then degrading and inducing it,
is a high hurdle in its own. Also, looking at the pipeline in the US, everyone is going to bispecifics rather than
ADCs. I think that this multi-specific antibody is probably the main thing.
That being said, the CD3s and such are pretty much filled up. I’m vaguely thinking that maybe you need to dosomething different. I’d appreciate any feedback on my thoughts if I’m wrong.
Also, ONO-4578 was my personal, one of the most promising stocks that Japanese companies are doing
among the cold to hot. You didn’t say anything on it, so I wonder what happened there. It has the most clinicalprograms. Could you please explain that first?
Takino: You are wondering what I think about the idea of drug targets or drug discovery trends in oncologythat you just mentioned. However, it is presumptuous for me to say something about it.

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I think it's not always a promising oncology drug discovery target for Cold to Hot or hard targets.
It is true that the number of hard targets is increasing, but recently I am positively thinking to some extent
that the width of drug discovery targets such as non-coding will spread more and more in the future. I would
like to emphasize that we are not pessimistic about the future of drug discovery targets.
Having said that, I think it is true that each one is still becoming more difficult and complicated. Therefore, I
think that the risk of limiting to one modality, as well as the point made earlier, are a double-edged sword. I
believe that if we keep our windows open widely and are able to use modalities with agility and master them,it will be a great advantage. It is a bit off topic.
I would like Mr. Idemitsu to comment on ONO-4578 later, but this time, we are here to talk about the efforts
and directions of new drug discovery in terms of open innovation. As we have compiled the information fromthe press releases, I would like to omit the issues related to ONO-4578 this time. I am sorry.
Idemitsu: Thank you very much for your attention on ONO-4578. We are in the middle of a PoC trial for various
cancer types. Please wait a little longer for the results.
We are hypothesizing that resistance to I-O can be lifted by antagonizing EP4. We hope you can wait a little
longer.
Questioner 5: Is it ok to assume that you will have some update on this around 2023 to 2024?
Idemitsu: About the timing of the result, I will be able to tell you when it is clear.
Questioner 5: Lastly, Itolizumab. If I look at GVHD, I think that Ruxolitinib or JAK2 are probably the mostrecently approved for acute GVHD. As you said, the complete response rate of these products is probably
around 30%, your data shows as it is. However, the number of patients is still small in your company, so thisis not enough to make a difference. Also, the dose response is not very clear, so I wonder if acute GVHD is a
bit risky.
Also, as for lupus nephritis, belimumab is proceeding, so yours is certainly much more effective comparing to
it. I think the definition of partial response and complete response is a little different over there, but I thinkit’s about 40% in terms of partial response. Your compound will probably get about 70% if you do it with them.
What I don’t understand well is I guess the UPCR was about 3.3. I think you need to set the same baseline as
used in the belimumab trial. Can I understand that yours is on the same baseline as in the trial of belimumab?
This is my last question.
Idemitsu: First of all, as for GVHD, the JAK inhibitor is now approved for second-line treatment, but not for
first-line treatment. It is true that the n number is less. For that reason, we now secure the option right towait for the results. Regarding lupus nephritis, I am not able to reply to your question because I have no baseline data on the UPCR at hand right now.
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