［Corporate Information］

When was the company founded？

Modalis Therapeutics Corporation was founded in Tokyo Japan in January 2016.
The consolidated subsidiary, Modalis Therapeutics Inc. was founded in Cambridge, Massachusetts USA in April 2016.

What does Modalis mean?

Modalis (pronounced “MO-DA-LIS”) is an original name that the Company has chosen to represent the Company’s proprietary gene modulation technology, CRISPR-GNDM, as a new modality (therapeutic technology) to assist patients fighting with genetic disorders. It is the key to treatment of genetic diseases, and the logo of the company name expresses “a gene switch” becoming the target of the CRISPR-GNDM technology.

What is Modalis’s scope of business?

You can see the outline of our business on the “Our Science” and “Business” pages.

The board of directors consists entirely of non-executive director other than the president, but what are your thoughts on the risks associated with the president running the execution just by himself?

Although all of our board of directors, with the exception of Mr. Morita, are non-executive director, our governance structure is similar more to the U.S. model, which is structured in such a way that directors and execution are separated and executive officers are delegated to execute the company’s operation.
The officers are currently three members: CEO who is in overall charge, CSO who oversees R&D, and CFO who oversees finance and administration. In addition, there are directors with relevant experience in pharma/biotech industries under them. So, we believe that we have a solid human resource base.
However, we also believe that strengthening our team structure is important for our future development, and we intend to continue to acquire excellent human resources.
(April 1, 2022)

What does US lab relocation mean to the company?

As of Oct 20, Modalis relocated its US operation to Waltham MA.
Since mid last year, the capacity of the US lab has become one of the limitation for our growth and we explored opportunities of relocation. But, due to supply-chain issues in US, our relocation had been pushed back by then.
With this relocation, we are able to accommodate process development function as well as further increase of research team. Thereby, we can expedite and deepen our product development including MDL-101.
The budget for this relocation was included in the plan for the current fiscal year.
(November 5, 2021)

What kind of employees are working in the U.S. laboratories?

The U.S. laboratory currently has approximately 30 people.
Of these, about 20 are involved in research and about 5 are involved in development, which consists of process development, preclinical, and project management. The rest are in administration.
The typical profile of research department personnel is that of a researcher with a Ph.D. and post-doctoral experience and a technician who had earned a master’s degree. Other mid-career personnel have experience in gene therapy research and development at pharmaceutical companies and other biotech companies.
(April 1, 2022)

［Financial］

When do you announce financial results?

We announce financial results following the end of every quarter. Please see the “IR Calendar” page.

When is the fiscal year end?

Annually on December 31st.

Where can I get copies of your past business results?

Please see the “Financial Results” page for past business results.

How can I check the video streaming of the briefing sessions?

We provide video streaming of our analyst meetings. Please see the video library available on our website.

Do you have any plans to disclose earnings forecasts or outlooks?

The earnings forecasts are not presented due to the difficulty of formulating reasonably accurate estimates at this time.

Do you have a timeline for turning a profit or making a leap forward at this point in time?

Since we do not disclose earnings forecasts, we cannot give a specific number of years as to when the company will become profitable.
We believe that the value inflection point shall come around 2024, considering the current pipeline status. This is because we are developing MDL101 based on the assumption that we will file IND in 2023 and interim results will be available within a short period of time after the start of clinical trials, as we have announced before. We believe that the pipeline that we are licensing out to our partners may also reach clinical trials at the same time, and the clinical results of these three pipelines should be enough to make a big leap forward. This does not preclude ample opportunities to earn upfront and milestone payments from the pipelines even before then.
(April 1, 2022)

When will the operating revenue be recognized？

Our major operating revenues consist of upfront and milestone payments in R&D collaborations, as well as revenue from clinical/sales milestones and royalties from license agreements. Each revenue is recorded as operating revenue when the contract is signed or when the conditions stipulated in the contract are met. As a result, our operating revenue is not reported monthly or quarterly but fluctuates depending on achievement of results.

From 2021 Q2 there are non-current liabilities reported. What are the details of this liability? Furthermore, what type of impact will this have on the business results?

Modalis has secured the CRISPR/Cas9 basic patent license (patent right) from Editas Medicine Inc (“Editas”). In 2021 Q2, a portion of the licensing fees were received from the out-licensing party. As a result, the amount is being reported as a non-current liability.

The non-current liability in question will depreciate in accordance with the duration of the licensing agreement, so the corresponding depreciation expense for the license (patent right) will be effectively offset on the PL Statement.
(August 5, 2021)

What is the impact of the rise in US interest rates and yen depreciation of against the US dollar?

Rise in U.S. interest rates:
Because we have no debt, we are not directly affected by interest payments.

Yen’s depreciation against the US dollar:
Since we have a laboratory in Massachusetts, US, where we conduct R&D, most of our payments are made in US dollars, so if the yen depreciates, our costs in Japanese yen will increase. On the other hand, if revenue is received on a dollar basis, the yen equivalent would increase, which would offset the future effect.
(November 7, 2022)

What are the “Key Audit Matters (KAM)” for the current fiscal year?

“Key audit matters (KAM)” are audit matters that the auditor determines to be of particular importance of the auditing company and are defined and described in the annual audit report.
The auditor makes a final judgment on the matters at the end of each fiscal year, so we are not in a position to tell what that will be for this year. That of last fiscal year was “Appropriateness of judgment on the necessity of recognition of impairment loss of non-current assets in the company’s gene therapy drug development business”. Please refer to the following for details.
March 29, 2022 “Audit Report on Current Consolidated Financial Statements” (bit.ly/edinetE35518)
Generally speaking, non-current assets may be fully or partially impaired if it is determined that they cannot be capitalized according to certain accounting rules. (For your note, as of 3Q 2022, the recorded fixed assets includes tangible fixed asset of 349 million yen, intangible fixed assets of 657 million yen, and liabilities corresponding to intangible assets of -292 million yen).
Since impairment is an accounting matter, there is no actual cash out, and business value and these assets themselves do not disappear even it is applied.
(November 7, 2022)

NEW!

Does the recorded impairment loss matter to the future business?

It doesn’t.
This was recorded in accordance with the “Accounting Standard for Impairment of Fixed Assets” because the Company is in the research and development phase of its pharmaceuticals business, and therefore, the profit and loss arising from operating activities are continuously negative, and future projections are highly uncertain in terms of profitability considering the characteristics of the business.
However, since this is a numerical figure in accordance with the accounting standards, the business value and the fixed assets themselves do not disappear, and the fixed assets can still be used to conduct business as before. There will be no actual cash outflow, so there will be no significant change in the business situation. In addition, as a result, the depreciation expense corresponding to the impaired fixed assets will be reduced from the next fiscal year onward.
(February 13, 2023)

NEW!

Why we marked “gain on reversal of advances received”?

We licensed the CRISPR/Cas9 basic patent from Editas Medicine Inc in 2020. In 2021, when we sublicensed the right to a partner, the partner paid a certain amount as a contribution to the license. The amount we received was booked as a liability for Advances Received on our B/S.
Along with the impairment loss marked this 4th quarter, the Advances Received in question and the corresponding asset, which is the right for the license, were offset both from the B/L.
As the result, the Advances Received was recorded as extraordinary gains.
(February 13, 2023)

［Stock Information & Shareholders Information］

On what exchange is the company listed?

Modalis listed on the Tokyo Stock Exchange Mothers on August 3, 2020 and on the Growth Market on April 4, 2022.

What is the stock code of Modalis?

4883

Do you plan to pay dividends?

We have not paid dividends since the establishment. As we will continue to carry out R&D activities that require large up-front investments, we will not pay dividends for the time being and will prioritize securing funds for continuing R&D activities.
We recognize that returning profits to shareholders is an important management issue. If the stable profit can be earned in the future and sufficient profit can be secured to cover R&D funds, we will also consider profit distribution after comprehensively considering the need to enhance internal reserves to prepare for R&D activities.

Do you currently have any preferential system for shareholders?

Not at the moment.

What is the number of shares constituting one trading unit of shares?

100 shares

Who do I contact to change share registration information such as ownership and changes of address?

Please contact your securities company.

When is the Ordinary General Meeting of Shareholder?

Annually in March.

Are there any plans to hire an IR person? Any chance we can get comments over the phone?

In our IR process, we accept questions only on our website (We do not respond to telephone inquiries), confirm all questions we receive, and answers to those that we believe need to be addressed are made public on our website and in disclosure documents. This is based on our policy that individual responses are not fair in terms of fair-disclosure, and that information that is deemed to require a response should be disclosed in a broad and fair manner. Therefore, we do not respond to individual inquiries by telephone or e-mail. We also do not offer tours of our offices or research facilities from security and confidentiality standpoints.
(April 1, 2022)

Other than during the announcement of financial results, do you release information/IR regarding the status of R&D activities (such as the NHP trial)?

The company is currently in R&D phase, so the release of IR regarding the status of individual pre-clinical R&D activities is restricted. Depending on the progress and expansion of future pipelines, we believe there may be increased opportunity for IR.

Moreover, regarding the status of individual R&D activities, we have decided that publicly disclosing this information is not favorable from a competition standpoint, as it could be advantageous for our competitors and could have a harmful impact on stock value in the long-term. Furthermore, when a license is being negotiated, details of the research status can be communicated only to the negotiating party, so restrictions on public disclosure are standard.

Disclosures regarding individual R&D activities occasionally give stockholders expectations which may have an excessive influence on the stock price. The company has decided to proactively disclose information that will have serious impacts for stockholders.

When the license-out agreement is concluded, will IR be conducted accordingly? Or will it be at the time of financial announcement?

In accordance with laws, regulations, and rules, we will proactively disclose important corporate information, such as contracts that have a significant impact on our business performance, to investors in a timely manner. While we are unable to say whether or not such information should be disclosed on an individual basis, we believe that important corporate information, such as license-out agreements, is subject to timely disclosure.

On the other hand, we are unable to disclose any unpublished information that we deem not to be in a situation to be disclosed, even if we receive inquiries about it.

Change in Policy on Non-Disclosure of Partnering Goals.

We had been disclosing our intention and target timing of partnering goals for our own pipelines because we believed it would contribute to investment information.
However, since partnering depends not only on the progress of the development and our intentions, but also on the intentions and strategies of the other party, we have determined that disclosing information that is not within our control is not appropriate for investment information.
In addition, disclosing our partnering intentions and deadlines would not have a positive impact on negotiations, and in fact there have been cases where such an impact has occurred. Therefore, we have decided not to disclose our partnering goals.
(August 5, 2022)

At what point in time are disclosures made about patents?

First, patents that are eligible for press-release must be patents that have a significant impact on our business, such as patents related to our pipelines, and the PR of such patents will not have a negative impact on our business.
In the case of a co-filed patent with a partner, only those patents that have been agreed upon will be disclosed. Therefore, not all patents are subject to disclosure. On the other hand, there are many resources that allow us to know the status of the patents. So it is possible for you to search by yourself if you wish.

Regarding timing, the process from the filing of a patent application to its registration is, in principle, one year and six months after the filing date, the application is published to the general public (application publication).
At this stage, the application is not yet granted, but the examination process continues, and the patent is granted by receiving a notice of allowance for those applications that pass the examination. After that, the application is officially registered as a patent after payment of a registration fee.
Typically, disclosure is made after receiving an examiner’s notice of allowance that the patent is certain to be registered to some extent.
(Published February 14, 2022, updated September 1, 2022)

Will Company continue to disclose each revision to the development plan?

It is our policy to disclose any significant changes in development plans through press releases or other means. In the case of ordinary revisions, our policy is to disclose such revisions in each quarter and at other times.
(September 15, 2022)

［Pipeline］

You had planned to license out MDL101 in the first half of 2022, how is the progress going?

Although we continue to have dialogues with potential partners, we are proceeding with our business with the belief that advancing development toward clinical trials as planned will ultimately add value to the program and technology and lead to the realization of an alliance on better terms.
Since the decision to enter into an alliance depends on the timing and intent of the other party as well as our own, it is not something that can be achieved solely through our efforts. On the other hand, as we recognized again at CureCMD conference, where we participated, MDC1A is a life-threatening disease, and given the current situation where the drug we are developing is a hope of the patients, the best thing we can do and manageable to us is to proceed with the development as fast as possible while we are waiting for a right partner who has strong commitment to develop the molecule together will make a decision at an appropriate time and under the appropriate conditions.
(August 5, 2022)

What is the reason for changing the AAV capsid at this time? And What is the advantages of the improved AAV.

The success of gene therapy since the 2010s has been largely due to adeno-associated virus (AAV) vectors, which are considered relatively safe and have a low risk as not self-replicating in the body mor inserting into chromosomes after transduction into cells. This was a major safety advantage over the previous generations.
Early gene therapies using AAV were developed initially for applications that requires local administration such as ophthalmology, and the remarkable results of these therapies have led to the expansion of their use to muscle diseases that require systemic high-dose administration. Currently, the pipelines of various companies for the treatment of Duchenne Muscular Dystrophy (DMD) are reaching to the late-stage clinical trials and regulatory submissions, and the results of clinical trials have led to discussions of various issues associated with large systemic dosing. To tackle these problems, academia and the pharmaceutical industry have developed improved AAV vectors with enhanced tropism to target tissues such as muscle, and several recently developed improved vectors have been confirmed to have more than 10-fold improved tropism and other characteristics compared to the conventional type.　These profiles are expected to have a disruptive impact in terms of reduced toxicity in off-target organs such as the liver and lower manufacturing costs due to lower dosage requirements.
Under these circumstances, we have come to believe that the significance of continuing development with the current technology is largely lost and that ethical issues arise in administering products developed based on the old technology, which has concerns, when there are new technologies with higher safety standards.
We believe that products developed based on new technologies are superior in terms of efficacy, safety, manufacturing cost, and probability of success, and that although this may temporarily delay development in the short term, it will have a positive impact in the long term by increasing product and corporate value.
(September 15, 2022)

Will modifying the MDL-101 AAV render the previous R&D effort useless?

No.
The GNDM molecule to be mounted on the improved version AAV capsid will be basically the same molecule as before, so the drug efficacy and safety data obtained to date will be extrapolatable.
Since GMP(Good Manufacturing Practice) manufacturing has not yet started, some process development will have to be redone to accommodate the new molecule, but we believe that this will require only minimal backtracking.
(September 15, 2022)

Does this affect the license-out of MDL-101?

There may be some potential impact on the partnering schedule, but on the other hand, we believe that the improved MDL-101 configuration will be more strongly supported by the partners, so we believe that the results will be positive.
(September 15, 2022)

Why company put higher priority on MDL-104, which has been a late starter?

Pipelines that require systemic administration, such as MDL-101, will be affected by the transition to improved AAV for the reasons described in Q1, but molecules that are intended for local administration to the CNS, such as MDL-104, MDL-205, and MDL-206, do not have the same risk.
When considering risk diversification of our pipeline portfolio, we believe it is reasonable to develop MDL-104 in parallel with MDL-101, as both have a different risk orientation.
Advantages of MDL-104 include: 1) local administration avoids systemic toxicity, 2) also local administration allows for much lower manufacturing of the clinically required dose, and 3) availability of humanized Tau mice that allows for direct estimation of clinical doses by mouse studies.
For the above and other reasons, the development timeline of MDL-104 could be shortened and becomes comparable to MDL-101 which will undergo improvements. As a result, we believe it makes sense to raise the priority of MDL-104.
(September 15, 2022)

What is the difference between MDL-206, which Modalis regained rights and put into internal program in August 2021, and the current MDL-204?

While both pipelines use the same CRISPR-GNDM® technology approach to create gene therapies, each program has its own technical challenges specific to the target gene, patient population size, and competition from other modalities.
In the case of MDL-206, the decision to continue the program as our own was based on reasons such as the target Angelman Syndrome’s affinity to the technology and the difficulty of approaching it with other modalities, as well as the assumed efficacy based on existing data. However, the decision to discontinue MDL-204 was based on a comprehensive judgment that it was not sufficiently superior or reasonable.
(January 7, 2022)

NEW!

Can you share why the joint research of MDL-205 was terminated and why it is being reacquired as an in-house pipeline?

At the end of the originally agreed-upon collaboration, we were unable to reach an agreement with our partner, Eisai, regarding an extension or transition to another arrangement.
Although the details of the agreement nor the target cannot be disclosed until the reacquisition agreement is completed, We believe that there is a high unmet medical need and a large number of patient population in this disease area and that the results of the joint research can be sufficiently differentiated from other approaches. We are grateful for this collaboration opportunity to our partner, which has deep knowledge and research resources in this field, and for the excellent results achieved.
(February 13, 2023)

Do you foresee any increase or decrease in the pipelines in the future?

We have several new candidates, including those for which we are currently exploring the possibility of collaboration and those that are being incubated in-house. We plan to promote these to the pipeline at an appropriate stage.
Among existing pipelines, we will promptly discontinue those for which we believe there is no longer a possibility to continue research and development, such as MDL-204.
We believe that it is reasonable to optimize the size and quality of our portfolio by conducting an appropriate metabolism.
We also believe that making decisions at an early stage, especially at the research stage, is effective in increasing the chances of success in the costly development stage.
(January 7, 2022)

［Our Business and R&D］

I understand that this is an industry where if you spend money in the business, the deficit may increase by that much, but what about using funds aggressively to advance development?

As one of our options, the company believes that the Company can reap more fruits by making a larger investment in R&D. On the other hand, the Company also believes that financial discipline is important.

To achieve financial discipline, by combining collaboration pipelines and the internal pipelines, Modalis aims to establish a “hybrid model” that benefits from early revenues from the collaboration pipeline and huge potential future profits from the internal pipeline.

The Company will aggressively invest more in our R&D within this framework of discipline.

Is it fair to assume that the market size for diseases with small patient numbers is small?

The market size of rare diseases is estimated by multiplying the number of patients by the drug price. However, since there are no existing drugs that can be used as a reference, it is hard to estimate drug. In addition, drug prices tend to increase inversely correlated with the number of patients, and therefore, the number of patients and the market size are not necessarily correlated.
(May 9, 2022)

How does the scale and process of manufacturing look like in product development for rare disorders?

Although you might imagine manufacturing scale for rare disease product is also small, it may not be the case for some of the genetic disorders. For instance, many type of muscular disorders require systemic injection and 1000L scale of production, which is a largest batch in many of the GTx manufacturing facilities, can produce products only for single digit to low 2-digit patients.
It is important to manufacture those products in a way that complies with GMP, and it makes sense for us to work with CDMO, which has experience, capability, and capacity to manufacture.
Our current strategy is to work with the CDMO which we made an alliance this time and revisit the strategy when we establish clinical PoC and risk is well mitigated.
(November 5, 2021)

Why are most of the diseases covered by the pipeline in the muscular and the neuro area? Can you target cancer?

AAV (adeno-associated virus) vectors are currently the predominant delivery tool for gene therapy for genetic diseases. This is because of their superiority in terms of delivery efficiency and safety. On the other hand, the flip side of safety is that the virus does not replicate in the delivered cells, so the effect is attenuated each time the cells divide. Thus, the effect will not persist in cells that are actively proliferating.
For this reason, regardless of our technology, potential targets for gene therapy using AAV are limited to organs and tissues with relatively inactive cell proliferation, and as a result, cells such as muscle and central nervous system cells are often targeted, while blood cells and cancer cells are avoided.
Also, in the case of cancer cells, if the vector is not delivered to close to 100% of the cells, the effect will be temporary because growth will occur again from the undelivered cancer cells which will grow.
Some gene and cell therapies target cancer, but in such cases, they do not target the cancer itself, but rather aim to increase cancer-killing cell activity by introducing genes into cancer-killing cells.
(November 7, 2022)

What does the sublicense deal of which Modalis and Astellas entered into certain CRISPR/Cas9 foundational patents for use in this second quarter mean to Modalis’ business?

This outcome was already contemplated under the terms of our existing license agreements for the two programs entered into in 2019 as well as under our business plan. The detail of the deal is not disclosed due to strategic reason. This was in line with our existing arrangements and our business plan and therefore this will not have impact on our business while this allows our partner, Astellas, and licensed products to pursue further development.
(August 5, 2021)

What is the future of your relationship with Astellas?

To date, we have conducted a total of five joint research projects with Astellas, two of which have resulted in licensing agreements.
With the conclusion of the MDL-204 collaboration, there are no ongoing research collaborations with Astellas. However, we continue to maintain a good relationship through collaboration on two licensed programs, MDL-201 and MDL-202, as well as exploring other collaboration opportunities.
We’ve confirmed that Astellas continues to explore the existing programs licensed to it, MDL-201 and MDL-202, currently in the pre- clinical stage.
(January 7, 2022)

I believe there are areas of the previous year’s plan that have not been achieved, and I would like to hear how you look back on that and what you think about the future outlook. In particular, I would like to know more about partnering.

With regard to partnering, we recognize that we have not been able to realize our previously stated goals. At the time we stated it, we had fundamentals and materials to negotiate with and partners to negotiate with that we believed was reachable, but partnering, on the other hand, is something with a partner, and we have not been able to achieve it due to the judgment of the other party.
While clarifying partnering goals is disclosed from the perspective of dialogue with investors, clearly too much about goals (time, deal size) is not desirable from the perspective of negotiation strategy because it tells our target to the counterparty.
We understand that some may be concerned that partnering, including MDL-101, has not been achieved in accordance with our previous goals, but we believe that it is only a matter of time, as the most important R&D to increase value is progressing well and discussions with interested companies are continuing.
(April 1, 2022)

How does the CDMO collaboration impacts on business?

Manufacturing is one of the important element to start clinical trial of MDL-101. As Modalis does not have large-scale manufacturing capability, it needs to be transferred to the other party. The agreement with the 1st tier CDMO allows us to get access to its vector system and capability for manufacturing AAV and paves the way for sample production for GLP studies and clinical trials.
(November 5, 2021)

What is AAV? And what is the relationship between AAV and CRISPR-GNDM®?

The Company’s method of administering therapeutics is envisioned to deliver our proprietary CRISPR-GNDM® in an adeno-associated virus (AAV) vector to target cells in the body.
In other words, AAV is a delivery tool that delivers CRISPR-GNDM® to target cells.
(September 15, 2022)

What does the presentation at ASGCT mean to Modalis?

The ASGCT is the largest gene therapy-related scientific organization in the world with approximately 5,000 members.
Last year’s annual meeting was held virtually but reportedly attended by approximately 6,800 people.
Every year, not only cutting-edge scientific findings are presented, but also pharmaceutical and regulatory aspects are discussed.
We believe that our presentation at this annual meeting is not only to showcase our progress, but also to share our knowledge with the academic community as part of our responsibility as a leader in Epigenetic Editing field.
(May 9, 2022)

Any outcomes from the presentation at ASGCT?

This year‘s ASGCT was our first opportunity to present our technology and developments at a scientific conference, and we believe our presentations attracted a great deal of attention. This is consistent with the fact that our approach is quite new and unique even in the the rapidly developing field of gene therapy and genome editing, as well as with the emergence of new companies advocating epigenome editing and gene regulation.
As a result, we have received several inquiries about partnerships, which we believe has been very positive for our future business.
(August 5, 2022)

What is the INTERACT meeting?

INitial Targeted Engagement for Regulatory Advice on CBER producTs (INTERACT) meeting is an informal non-binding consultation with the Center for Biologics Evaluation and Research (CBER) at FDA.
This in an opportunity for a sponsor (developer) that develops a cutting-edge product, to obtain consultation on innovative investigational products associated with unique challenges.
Considering recent low acceptance rate of the meeting, we believe our product is innovative enough to get attention of FDA.
The goal of the meeting for us is to clarify a path toward the clinic of not just MDL-101 but whole products based on CRISPR-GNDM® technology.

For more info, please visit FDA site
https://www.fda.gov/vaccines-blood-biologics/industry-biologics/interact-meetings
(May 9, 2022)

How did the INTERACT meeting go?

This meeting was the first opportunity for MDL-101 and CRISPR-GNDM technology to make a contact with the regulatory authorities.
While we do not have a policy for disclosing details, the meeting resulted in a better understanding on our part of
1. The position of the product and technology in gene therapy and applicable guidelines
2. Issues related to bridging the investigational drug with the product to be used in the GLP studies
3. Data to be demonstrated in the IND package
4.The rationale for the study design that we should present in the Pre-IND
As a result, the FDA’s opinion is generally consistent with our original study design, and we do not believe that we need to make any significant changes to our study plan or strategy.

Refer to following for INTERACT meeting
https://www.fda.gov/vaccines-blood-biologics/industry-biologics/interact-meetings
(August 5, 2022)

Can you elaborate a little more about the Utrophin patent?

This patent is for a therapeutic concept and molecules that uses GNDM technology to treat DMD. The treatment is based on a mechanism that supplements mis-functioning Dystrophin gene in patients by upregulating the expression of the fetal/juvenile form of the gene, Utrophin. The cDNA of the Dystrophin gene is 14 kbp, too large to be carried in an AAV vector, and this is a target that takes advantage of the GNDM, which is gene size agnostic. No disclosure is made for the collaboration program as to which patents correspond to which programs.
(May 9, 2022)

How does the USPTO’s Notice of Allowance to UTRN patent impacted on Modalis’ business?

The fact that the patent will be granted in the U.S. following Japan means that the product will be protected by the patent when the pharmaceutical product based on the patent is launched in that country. Therefore, we believe that the granting of the patent in the U.S., which is believed to account for about half of the pharmaceutical market, is of great significance.
We will continue to work with our partners to obtain patents in the remaining target countries.
(August 5, 2022)

During the second quarter, the UTRN patent was granted in the United States. Was it issued?

Yes, the patent was issued in October 2022.

As for the flow of patent examination, once a patent is granted, the patent is issued by paying the issue fee. Therefore, if there is an IR for a grant of a patent, we hope that you will understand that the patent will be granted over time.
(November 7, 2022)

I saw Modalis was posting a job of ophthalmology expert in the U.S. Does this mean that company has plan to enter ophthalmology field?

It is true that we were looking for a researcher in the field of ophthalmology. This is to explorer ophthalmologic opportunities as part of the central nervous system and does not mean that we are specifically exploring new areas.
(April 1, 2022)

Several epigenetic modulation companies were established at the end of last year, will this affect the competitive environment?

We are delighted to see that epigenetic modulation is now widely recognized as an effective drug discovery technique.
The Company believes that, in addition to the protection provided by our existing intellectual property, we can continue to maintain our leading position by based on the collective experience we have gained in the six years since our establishment.
(February 14, 2022)

Does the outcome of CTGTAC meeting impact on Modalis’ development?

FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) held a meeting on September 2nd and 3rd, 2021
This was to discuss the toxicity risks of adeno-associated virus (AAV) vector-based gene therapy product.
The meeting was held in response to toxicities observed in animals and humans after administration of gene therapy products including (1) hepatoxicity, (2) Thrombotic Microangiopathies (TMA), (3) Dorsal Root Ganglia neuronal loss, (4) brain MRI abnormalities, and (5)AAV vector integration and oncogenicity. We understand that the objective of the meeting was to provide recommendations for strategies to minimize the risk to patients receiving gene therapy products.
This will not significantly affect our development guidelines or timeline as most of the toxicities are not new to us and we have set up certain countermeasures, but we will take appropriate action based on our understanding of the authorities’ awareness of the issue.
The Company has been following up on necessary regulatory guidance, reports, meetings, and the latest papers related to gene therapy in a fairly extensive and timely manner, including this meeting, so the information can be reflected in the Company’s strategy as needed.
(February 14, 2022)

How does Broad’s victory in the U.S. patent interferences proceeding affect Modalis’ business?

The U.S. Patent Office (USPTO) had been conducting an interferences (#106,115) between Broad Institutes (Broad) and the University of California, the University of Vienna, and Dr. Emmanuelle Charpentier (collectively, CVC), challenging the prior inventions in the U.S. On February 28, 2022, the USPTO Board of Appeals (PTAB) ruled that Broad’s rights were not effectively interfered with in this interferences.
On February 28, 2022, the PTAB ruled in favor of Broad, holding that there was no interference in fact with the interferences.
The PTAB also rejected the CVC’s argument in No. 106,048, which was also the subject of an earlier interferences proceeding.
This indicates that Broad’s patent application for genome editing technology in eukaryotes, including humans, is valid in the United States.
As a result, the CRISPR foundational patents, which we have a right through the license agreement with Editas, will continue to be valid in our business areas and will continue to secure our business.
(May 9, 2022)

Is there any impact of the draft guidance to gene editing product published by FDA in Mar?

This Draft Guidance reflects the FDA’s findings in response to the recent progress of several genome-editing therapeutics to the clinical stage and is intended for companies primarily in preclinical stage.
The products we are developing are considered to fall under this category in a broad sense and we believe that the clarification of the hurdles to the start of clinical trials in this manner will make it easier for developers, including us, to plan preclinical strategies and to develop products.
We do not see any new hurdles in this guideline that we did not anticipate.

For more info, please visit FDA site.
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/human-gene-therapy-products-incorporating-human-genome-editing
(May 9, 2022)

［Other］

Dose the professor Nureki’s step down matter to business and technology development?

Not at all.

The initial development of the CRISPR-GNDM® technology has already completed and necessary technologies and licenses have been transferred to the company far before the separation.
Additional technology development is being conducted 100% by the company and there is nothing we need to rely on Univ. Tokyo.
(November 5, 2021)

“Gene therapy” is noted in the Kishida Cabinet’s policy published on 6/7. What impact does this have?

We understand that budgetary and legal measures will be taken based on this decision, and the impact of this decision is still unknown at this time.
However, the fact that the areas in which we operate are related to the national interest and have been identified as priority areas in which to provide incentives is a tailwind, but not a headwind, for our business. Hopefully, appropriate selection will be made and budget allocations will be made among these areas.

Reference: Basic Policy on Economic and Fiscal Management and Reform 2022
https://www5.cao.go.jp/keizai-shimon/kaigi/cabinet/2022/summary_en.pdf
(August 5, 2022)

Do you sell novelties such as Modalis T-shirts?

Branded goods are not for sale and are for internal use only.