2 unchanged sentences
We are headquartered in New York City with our main operations in Gräfelfing near Munich, Germany.
−Removed: We had 77 employees as of February 1, 2024.
+Added: We had 91 employees as of March 1, 2025.
We are pursuing clinical development of orally administered, small molecule programs, each of which has unique features intended to directly address the unmet needs of patients with serious chronic inflammatory and autoimmune diseases.
−Removed: These include the vidofludimus calcium (IMU-838) program, which is in Phase 3 clinical development for patients with multiple sclerosis (“MS”) and which has shown therapeutic activity in Phase 2 clinical trials in patients suffering from relapsing-remitting MS, progressive MS and moderate-to-severe ulcerative colitis (“UC”);
−Removed: the IMU-856 program, which is targeted to regenerate bowel epithelium and restore intestinal barrier function, which could potentially be applicable in numerous gastrointestinal diseases, such as celiac disease, inflammatory bowel disease (“IBD”), short bowel syndrome and irritable bowel syndrome with diarrhea;
+Added: These include the vidofludimus calcium (IMU-838) program, which is in Phase 3 and Phase 2 clinical development for patients with relapsing and progressive multiple sclerosis (“MS”), respectively, and which has shown therapeutic activity in Phase 2 clinical trials in patients suffering from relapsing-remitting MS (“RRMS”), progressive MS and moderate-to-severe ulcerative colitis (“UC”);
+Added: the IMU-856 program, which is targeted to regenerate bowel epithelium and restore intestinal barrier function, which could potentially be applicable in numerous gastrointestinal diseases, such as celiac disease, inflammatory bowel disease (“IBD”), Graft-versus-Host-Disease ("GvHD") and weight management;
and the IMU-381 program, which is a next generation molecule being developed to specifically address the needs of gastrointestinal diseases.
The following table summarizes the potential indications, clinical targets and clinical development status of our three product candidates:
−Removed: Our most advanced drug candidate, vidofludimus calcium (IMU-838), is being tested in several ongoing MS trials as part of its overall clinical program in order to support a potential approval for patients with MS in major markets.
+Added: Our most advanced drug candidate, vidofludimus calcium (IMU-838), is being tested in several ongoing MS trials as part of its overall clinical program in order to support potential approvals for patients with MS in major markets.
The Phase 3 ENSURE program of vidofludimus calcium in relapsing multiple sclerosis (“RMS”), comprising twin studies evaluating efficacy, safety, and tolerability of vidofludimus calcium versus placebo, and the Phase 2 CALLIPER trial of vidofludimus calcium in progressive multiple sclerosis (“PMS”), designed to corroborate vidofludimus calcium’s neuroprotective potential, are ongoing.
On October 9, 2023, we announced positive interim data from the CALLIPER trial, showing biomarker evidence that vidofludimus calcium’s activity extends beyond the previously observed anti-inflammatory effects, thereby further reinforcing its neuroprotective potential.
−Removed: Top-line data from the CALLIPER trial, for which the recruitment of in total 467 patients was completed in August 2023, is expected to be available in April 2025.
−Removed: Moreover, we currently expect to report an interim futility analysis of the ENSURE program in late 2024 and to read-out the first of the ENSURE trials in the second quarter of 2026.
+Added: Top-line data from the CALLIPER trial, for which the recruitment of 467 total patients was completed in August 2023, is expected to be available in April 2025.
+Added: Moreover, on October 22, 2024, we announced a positive outcome of an interim analysis of the ENSURE program, with an unblinded Independent Data Monitoring Committee ("IDMC") confirming that the predetermined futility criteria have not been met and recommending that both ENSURE trials should continue without changes, including no need for a potential increase of the sample size.
+Added: Completion of the first of the ENSURE trials is currently anticipated in the second quarter of 2026;
+Added: and the completion of the second ENSURE trial in the second half of 2026.
Although we currently believe that each of these goals is achievable, they are each dependent on numerous factors, most of which are not under our direct control and can be difficult to predict.
We plan to periodically review this assessment and provide updates of material changes as appropriate.
−Removed: If approved, we believe that vidofludimus calcium, with combined neuroprotective, anti-inflammatory, and antiviral effects, has the potential to be a unique treatment option targeted to the complex pathophysiology of MS.
+Added: If approved, we believe that vidofludimus calcium, with combined neuroprotective, anti-inflammatory, and antiviral effects as well as a favorable safety and tolerability profile, has the potential to be a unique treatment option targeted to the complex pathophysiology of MS.
Preclinical data showed that vidofludimus calcium activates the neuroprotective transcription factor nuclear receptor-related 1 (“Nurr1”), which is associated with direct neuroprotective properties and may enhance the potential benefit for patients.
1 unchanged sentence
This mechanism is associated with the anti-inflammatory and antiviral effects of vidofludimus calcium.
−Removed: We believe that the combined mechanisms of vidofludimus calcium are unique in the MS space and support the therapeutic performance shown in our Phase 2 EMPhASIS trial in relapsing-remitting MS patients, in particular, via data illustrating the potential to reduce magnetic resonance imaging (“MRI”) lesions, prevent relapses, reduce the rate of disability progression, and reduce levels of serum neurofilament light chain (“NfL”), an important biomarker of neuronal damage.
−Removed: Vidofludimus calcium has shown in clinical trials reported to date a consistent pharmacokinetic, safety and tolerability profile and has already been exposed to more than 1,800 human subjects and patients in either of the drug’s formulations.
+Added: We believe that the combined mechanisms of vidofludimus calcium are unique in the MS space and support the therapeutic performance shown in our Phase 2 EMPhASIS trial in RRMS patients, in particular, via data illustrating the potential to reduce magnetic resonance imaging (“MRI”) lesions, prevent relapses, reduce the rate of disability progression, and reduce levels of serum neurofilament light chain (“NfL”), an important biomarker of neuronal damage.
+Added: Vidofludimus calcium has shown a consistent pharmacokinetic, safety and tolerability profile in clinical trials reported, to date, and has already been exposed to approximately 2,700 human subjects and patients in either of the drug’s formulations.
IMU-856 is an orally available and systemically acting small molecule modulator that targets Sirtuin 6 (“SIRT6”), a protein which serves as a transcriptional regulator of intestinal barrier function and regeneration of bowel epithelium.
−Removed: Based on preclinical data, we believe this compound may represent a unique treatment approach, as the mechanism of action targets the restoration of the intestinal barrier function and bowel wall architecture in patients suffering from gastrointestinal diseases such as celiac disease, IBD, short bowel syndrome, irritable bowel syndrome with diarrhea and other intestinal barrier function associated diseases.
+Added: Based on preclinical data, we believe this compound may represent a unique treatment approach, as the mechanism of action targets the restoration of the intestinal barrier function and bowel wall architecture in patients suffering from gastrointestinal diseases such as celiac disease, IBD, GvHD and other intestinal barrier function associated diseases.
Based on preclinical investigations demonstrating no suppression of immune cells, IMU-856 may have the potential to maintain immune surveillance for patients during therapy, which would be an important advantage versus immunosuppressive medications and may allow the potential for combination with available treatments in gastroenterological diseases.
−Removed: Data from the final portion of a Phase 1 clinical trial in celiac disease patients during periods of gluten-free diet and gluten challenge demonstrated positive effects for IMU-856 over placebo in four key dimensions of celiac disease pathophysiology:
+Added: Data from a Phase 1b clinical trial in celiac disease patients during periods of gluten-free diet and gluten challenge demonstrated positive effects for IMU-856 over placebo in four key dimensions of celiac disease pathophysiology:
protection of the gut architecture, improvement of patients’ symptoms, biomarker response, and enhancement of nutrient absorption.
IMU-856 was also observed to be safe and well-tolerated in this trial.
−Removed: We are currently preparing clinical Phase 2 testing of IMU-856 in patients with ongoing active celiac disease (“OACD”) despite gluten-free diet, while also considering further potential clinical applications in other gastrointestinal disorders.
+Added: In a post hoc analysis of this Phase 1b clinical trial, IMU-856 demonstrated a dose-dependent increase of endogenous glucagon-like peptide-1 (“GLP-1”) levels.
+Added: IMU-856 also showed a dose-dependent reduction of body weight gain and food consumption in preclinical in vivo testing.
+Added: These two effects may indicate the potential for IMU-856 as an oral treatment option for weight management.
+Added: Contingent on financing, licensing or partnering, we are currently preparing clinical Phase 2 testing of IMU-856 in patients with ongoing active celiac disease (“OACD”) despite gluten-free diet, while also considering further potential clinical applications in other gastrointestinal disorders.
Immunic has selected IMU-381 as a development candidate to specifically address the needs of gastrointestinal diseases.
3 unchanged sentences
We expect to continue to lead most of our research and development activities from our Gräfelfing, Germany location, where dedicated scientific, regulatory, clinical and medical teams conduct their activities.
−Removed: Due to these teams' key relationships with local and international service providers, we anticipate that this will result in more timely and cost-effective execution of our development programs.
+Added: Due to these teams' key relationships with local and international service providers, we anticipate that this should result in more timely and cost-effective execution of our development programs.
In addition, we are using our subsidiary in Melbourne, Australia to perform research and development activities in the Australasia region.
−Removed: We also conduct preclinical work in Halle/Saale, Germany through a collaboration with the Fraunhofer Institute.
−Removed: Our business, operating results, financial condition and growth prospects are subject to significant risks and uncertainties, including the failure of our clinical trials to meet their endpoints, failure to obtain regulatory approval and failure to obtain needed additional funding on acceptable terms, if at all, to complete the development and commercialization of our three development programs.
+Added: We also conduct preclinical work in our laboratory in Martinsried, Germany and in Halle/Saale, Germany through a collaboration with the Fraunhofer Institute.
+Added: Our business, operating results, financial condition and growth prospects are subject to significant risks and uncertainties, including delays in clinical trials, the failure of our clinical trials to meet their endpoints, failure to obtain regulatory approval and failure to obtain needed additional funding on acceptable terms, if at all, to complete the development and commercialization of our three development programs.
We are focused on the development of new molecules that maximize the therapeutic benefits for patients by uniquely addressing biologically relevant immunological targets.
2 unchanged sentences
We are currently focused on maximizing the potential of our development programs through the following strategic initiatives:
−Removed: • Executing the ongoing Phase 3 ENSURE and Phase 2 CALLIPER clinical trial programs of vidofludimus calcium in RMS and PMS, respectively.
−Removed: • Executing the IMU-856 development program, including preparation of a Phase 2 clinical trial, in patients with OACD.
−Removed: • Continuing preclinical research to complement the existing clinical activities, explore additional indications for future development and generating additional molecules for potential future development.
+Added: • Executing the ongoing Phase 3 ENSURE clinical trials of vidofludimus calcium in RMS.
+Added: • Completing the Phase 2 CALLIPER clinical trial of vidofludimus calcium in PMS.
+Added: • Executing the IMU-856 development program, including preparation of a Phase 2 clinical trial.
+Added: • Continuing preclinical research to complement the existing clinical activities, explore additional indications for potential future development and generating additional molecules for potential future development.
• Facilitating readiness for potential commercial launch of our product candidates through targeted and stage-appropriate pre-commercial activities.
2 unchanged sentences
We have no products approved for commercial sale and have not generated any revenue from product sales.
−Removed: We have never been profitable and have incurred operating losses in each year since our inception in 2016.
−Removed: We have an accumulated deficit of approximately $410.9 million and $317.3 million as of December 31, 2023 and December 31, 2022, respectively.
+Added: We have never been profitable and has incurred operating losses in each year since inception in 2016.
+Added: We have an accumulated deficit of approximately $511.4 million as of December 31, 2024 and $410.9 million as of December 31, 2023.
Substantially all of our operating losses resulted from expenses incurred in connection with our research and development programs and from general and administrative costs associated with our operations.
1 unchanged sentence
We expect that our operating losses will fluctuate significantly from quarter-to-quarter and year-to-year due to timing of development programs.
−Removed: From inception through January 31, 2024, Immunic has raised net cash of approximately $431.4 million from private and public offerings of preferred and common stock.
−Removed: As of December 31, 2023, the Company had cash and cash equivalents of approximately $46.7 million.
−Removed: On January 4, 2024, we raised net cash proceeds in a private placement of approximately $75.0 million.
−Removed: With these funds we expect to be able to fund our operations beyond twelve months from the date of the issuance of the accompanying consolidated financial statements.
+Added: From inception through December 31, 2024, we have raised net cash of approximately $430.9 million from private and public offerings of preferred stock, common stock, pre-funded warrants and tranche rights.
+Added: As of December 31, 2024, we had cash and cash equivalents of approximately $35.7 million.
+Added: With these funds, we do not have adequate liquidity to fund our operations for at least twelve months from the issuance of these consolidated financial statements without raising additional capital, but such actions are not solely within the control of the Company.
+Added: If the Company is unable to obtain additional capital, it would have a material adverse effect on the operations of the Company, its clinical development program, and the Company may have to cease operations altogether.
+Added: These factors raise substantial doubt about the Company’s ability to continue as a going concern.
Key Status Updates
−Removed: Private Placement of up to $240 Million
−Removed: On January 4, 2024, we entered into a securities purchase agreement with select accredited investors to purchase shares of common stock (or pre-funded warrants in lieu thereof) in a three-tranche private placement offering.
−Removed: The first tranche was an upfront payment of $80 million at $1.43 per share and closed on January 8, 2024.
−Removed: The second tranche is a mandatory purchase of an additional $80 million of shares of common stock (or pre-funded warrants) at $1.716 per share, representing 120% of the first tranche purchase price and is conditioned on the announcement of Phase 2b topline data for CALLIPER trial, volume weighted average share price levels, and minimum trading volumes.
−Removed: A third tranche, to occur no later than three years after the second tranche, provides for the issuance of $80 million of shares of common stock (or pre-funded warrants in lieu thereof) at the same price per share as the second tranche, but permits investors to fund their purchase obligations on a “cashless” or net settlement basis, which would reduce the proceeds to be raised in the financing.
−Removed: The third tranche is conditioned on the same volume weighted average share price levels and minimum trading volumes as the second tranche.
−Removed: Assuming that the second tranche is exercised, and depending on the extent to which the investors elect to fund the third tranche through a net settlement basis, total gross proceeds from the offering to the Company would be between $160 and $240 million.
−Removed: The financing was led by BVF Partners L.P., and included participation from new and existing investors, including Avidity Partners, Janus Henderson Investors, Soleus Capital, RTW Investments and Adage Capital Partners LP.
−Removed: Partners acted as the lead placement agent and Ladenburg Thalmann acted as a placement agent in connection with the offering.
+Added: Private Placement of up to $240 Million (the "January 2024 Financing")
+Added: On January 4, 2024, Immunic entered into a Securities Purchase Agreement with select accredited and institutional investors, pursuant to which the Company agreed to issue and sell to the Investors in a three-tranche private placement shares of the Company’s common stock, $0.0001 par value per share or in lieu thereof, pre-funded warrants to purchase shares of Common Stock.
+Added: The Pre-Funded Warrants are exercisable immediately for $0.0001 per share until exercised in full.
+Added: • The first tranche, which closed on January 8, 2024, resulted in the purchase by the Investors of an aggregate of $80 million of Common Stock (or pre-funded warrants) from the Company at a price of $1.43 per share;
+Added: • The second tranche is a conditional mandatory purchase by the Investors of an additional $80 million of Common Stock (or pre-funded warrants) from the Company at a price of $1.716 per share, equal to 120% of the price paid in the first tranche and is subject to the satisfaction of three conditions:
+Added: ◦ release by the Company of topline data from its Phase 2b clinical trial of vidofludimus calcium (IMU-838) in progressive multiple sclerosis, which data is currently expected in or around April 2025;
+Added: ◦ the 10-day volume-weighted average price of the Common Stock is at least $8.00 per share during the 6 months following the data release;
+Added: ◦ aggregate trading volume during the same 10-day period is at least $100 million.
+Added: • The third tranche must occur no later than three years after the second tranche and is conditioned on the same volume-weighted average share price and minimum trading volumes as the second tranche.
+Added: The third tranche provides for the issuance of $80 million of shares of common stock (or pre-funded warrants) at the same price per share as the second tranche, but permits investors to fund their purchase obligations on a “cashless” or net settlement basis, which would reduce the cash proceeds to be raised by the Company in the January 2024 Financing.
+Added: Any of the conditions in the second or third tranches can be waived by holders of a majority of the outstanding securities (including the lead investor).
+Added: The fair value methodology used by the Company assumed the conditions will be waived if the trading price of the stock exceeds the purchase price.
+Added: The January 2024 Financing resulted in gross proceeds to the Company of approximately $80 million in the first tranche, and an additional $80 million if and when the second tranche occurs.
+Added: If the second tranche is completed and conditions for the third tranche are satisfied or waived, the Company could receive up to an additional $80 million in the third tranche.
+Added: However, the amount of cash received in the third tranche would depend on the extent to which the Investors elect to fund the third tranche through a “cashless” or net settlement basis.
+Added: Therefore, total gross proceeds from the offering to the Company could actually be between $80 million and $240 million.
+Added: Gross proceeds to the Company will be reduced by fees paid to the placement agents, capital markets advisors and payments of transaction expenses.
+Added: The Company intends to use the net proceeds from the January 2024 Financing to fund the ongoing clinical development of its three lead product candidates, vidofludimus calcium (IMU-838), IMU-856 and IMU-381, and for other general corporate purposes.
+Added: As of the closing date of the transaction of January 8, 2024, the Company did not have enough authorized shares to be able to issue the potential shares for tranche 2 and tranche 3 (collectively referred to hereafter as "the tranche rights").
+Added: Therefore, the Company recorded the value associated to the tranche rights as a liability of $23.6 million and allocated the remainder of the $80 million received (or approximately $56.4 million) from the common stock and pre-funded warrants to equity.
+Added: On March 4, 2024, at a special meeting of stockholders, the stockholders voted to increase the Company's authorized common shares from 130 million to 500 million shares.
+Added: As a result of the ability to issue shares in satisfaction of the tranche rights, the instrument was reclassified to stockholders' equity.
+Added: The Company allocated the transaction cost across the instruments on a relative fair value basis.
+Added: As a result, $4.0 million was netted against the equity proceeds and $1.7 million was recorded in other expense in the Consolidated Statements of Operations for the year ended December 31, 2024.
+Added: The January 2024 Financing was led by BVF Partners L.P., and included participation from new and existing investors, including Avidity Partners, Janus Henderson Investors, Soleus Capital, RTW Investments and Adage Capital Partners LP.
+Added: Leerink Partners acted as the lead placement agent and Ladenburg Thalmann acted as a placement agent in connection with the offering.
Piper Sandler, B.
Riley Securities and Brookline Capital Markets, a division of Arcadia Securities, LLC, acted as capital markets advisors to the Company.
−Removed: Notice of Allowance for United States Patent Protecting Vidofludimus Calcium's Dosing Regimens in Multiple Sclerosis
−Removed: On November 21, 2023, we announced that we have received a Notice of Allowance from the United States Patent and Trademark Office (“USPTO”) for patent application 17/992,162, entitled, “Compounds and Dosage Regimen for Use in the Prevention or Treatment of Chronic Inflammatory and/or Autoimmune Diseases.” Specifically, the resulting patent covers dosing regimens associated with vidofludimus calcium and other salt forms as well as free acid forms for the treatment of MS, including all regimens tested in the company’s MS clinical program.
−Removed: The patent is expected to provide protection into 2038, unless extended further.
−Removed: The patent was previously granted to us in Japan and certain other countries.
−Removed: Notice of Allowance for United States Patent Protecting the Treatment of Relapsing Multiple Sclerosis with Vidofludimus and Its Salts
−Removed: On November 2, 2023, we announced that we have received a Notice of Allowance from the USPTO for patent application 17/391,442, entitled, “Treatment of Multiple Sclerosis Comprising DHODH Inhibitors,” covering a daily dose of about 10 mg to 45 mg of vidofludimus calcium and other salt as well as free acid forms for the treatment of RMS.
+Added: The Company registered for resale by the investors in the January 2024 Financing up to 55,944,850 shares of common stock issued (or issuable upon exercise of pre-funded warrants) in the first tranche.
+Added: The Company will not receive any proceeds from the sale of these shares of common stock.
+Added: These shares are registered on a registration statement on Form S-3 (registration No.
+Added: 333-277040), which was declared effective by the SEC on April 30, 2024.
+Added: Notice of Allowance for Composition-of-Matter Patent of a Specific Polymorph of Vidofludimus Calcium in the United States
+Added: On March 20, 2024, we announced Notice of Allowance from the United States Patent and Trademark Office (“USPTO”) for patent application 16/981,122, entitled, “Calcium salt polymorphs as anti-inflammatory, immunomodulatory and anti-proliferative agents,” covering the composition-of-matter of a specific polymorph of vidofludimus calcium and a related method of production of the material.
The claims are expected to provide protection into 2041, unless extended further.
−Removed: Positive Interim Data from Phase 2 CALLIPER Trial of Vidofludimus Calcium in Progressive Multiple Sclerosis
−Removed: On October 9, 2023, we announced positive interim data from our Phase 2 CALLIPER trial of vidofludimus calcium in patients with PMS.
−Removed: The predefined interim analysis examined the change from baseline to 24 weeks in serum NfL and glial fibrillar acidic protein ("GFAP") levels among approximately the first half of patients enrolled in this trial.
−Removed: We believe that this data showed biomarker evidence that vidofludimus calcium's activity extends beyond the previously observed anti-inflammatory effects, thereby further reinforcing its neuroprotective potential.
−Removed: Serum NfL responses were consistently observed for vidofludimus calcium across progressive MS disease and all subpopulations.
−Removed: In the overall PMS population at 24 weeks (N=203), vidofludimus calcium was associated with a 6.7% reduction from baseline in serum NfL, compared to a 15.8% increase over baseline in placebo (p=0.01, post hoc).
−Removed: At 48 weeks (N=79), vidofludimus calcium reduced serum NfL by 10.4% from baseline, compared to a 6.4% increase in placebo.
−Removed: Substantial reductions were also seen across all PMS subtypes, as well as in patients that show or do not show disease and/or MRI activity.
−Removed: Although early, interim GFAP data also showed a promising signal:
−Removed: at 24 weeks (N=203), GFAP increased by 3.7% for vidofludimus calcium, and 4.4% for placebo.
−Removed: At 48 weeks (N=79), the change was only 2.7% for vidofludimus calcium, with a 6.4% increase for placebo.
−Removed: Progression of GFAP response is generally thought to evolve more slowly than NfL, and we believe that a longer follow-up may further strengthen this signal.
−Removed: Completion of Enrollment of Phase 2 CALLIPER Trial of Vidofludimus Calcium in Progressive Multiple Sclerosis
−Removed: On August 17, 2023, we announced completion of enrollment of our Phase 2 CALLIPER trial of vidofludimus calcium in patients with PMS.
−Removed: In total, 467 patients with primary PMS, or active or non-active secondary PMS have been randomized to either 45mg of vidofludimus calcium or placebo.
−Removed: A top-line data readout of the full 467 patients is expected in April 2025.
−Removed: Vidofludimus Calcium Acts as Potent Nurr1 Activator, Reinforcing Neuroprotective Potential in MS
−Removed: On May 17, 2023, we announced the publication of preclinical data showing that vidofludimus calcium acts as a potent Nurr1 activator, in addition to its known mode of action as a DHODH inhibitor.
−Removed: Activation of Nurr1 could be responsible for the drug’s postulated neuroprotective effects and may contribute to the previously reported reduction of confirmed disability worsening events in MS patients.
−Removed: Specifically, preclinical data shows potent Nurr1 activation by vidofludimus calcium at low concentrations in several test systems.
−Removed: The data was published in the peer-reviewed, high impact Journal of Medicinal Chemistry, in a paper entitled, “Development of a potent Nurr1 agonist tool for in vivo applications” (Vietor et al., 2023).
−Removed: Presentation of Clinical and Preclinical Data for IMU-856 at Digestive Disease Week 2023, Including Its Molecular Mode of Action
−Removed: On May 6, 2023, we announced the presentation of clinical and preclinical data for IMU-856 as a virtual e-poster at Digestive Disease Week 2023.
−Removed: Included in this presentation were new data on IMU-856’s mode of action as a potent modulator of SIRT6, a protein which serves as a transcriptional regulator of intestinal barrier function and regeneration of bowel epithelium.
−Removed: Positive Results From Phase 1b Clinical Trial of IMU-856 in Celiac Disease
−Removed: On May 4, 2023, we announced positive results from our Phase 1b clinical trial of IMU-856 in patients with celiac disease.
−Removed: The data demonstrated positive effects for IMU-856 over placebo in four key dimensions of celiac disease pathophysiology:
−Removed: protection of the gut architecture, improvement of patients’ symptoms, biomarker response, and enhancement of nutrient absorption.
−Removed: IMU-856 was also observed to be safe and well-tolerated in this trial.
−Removed: We believe that this data set provides initial clinical proof-of-concept for an entirely new therapeutic approach to gastrointestinal disorders by promoting regeneration of bowel architecture.
−Removed: The data provides first clinical evidence that IMU-856’s ability, observed in preclinical studies, to induce physiological gut cell renewal translates into clinical benefits for patients with celiac disease.
−Removed: Most importantly, the observed protection of intestinal villi from gluten-induced destruction, independent of targeting immune mechanisms involved specifically in celiac disease, appears to be unique among proposed therapeutic approaches and may be applicable to other gastrointestinal diseases such as IBD, short bowel syndrome and irritable bowel syndrome with diarrhea.
−Removed: Positive Data from Maintenance Phase of Phase 2 CALDOSE-1 Trial of Vidofludimus Calcium in Moderate-to-Severe UC
−Removed: On April 5, 2023, we reported positive data from the maintenance phase of our Phase 2b CALDOSE-1 trial of vidofludimus calcium in patients with moderate-to-severe UC.
−Removed: The data showed a dose-linear increase in clinical remission as compared to placebo at week 50.
−Removed: Moreover, an exploratory statistical analysis confirmed the 30 mg dose of vidofludimus calcium to be statistically superior (p=0.0358) in achieving clinical remission at week 50, with a 33.7% absolute improvement over placebo.
−Removed: A similar effect on clinical remission rates at week 50 was also found among those patients who received corticosteroids during the induction phase.
−Removed: Finally, a dose-linear increase in endoscopic healing was observed, with the 30 mg dose of vidofludimus calcium being associated with a 37.8% absolute improvement over placebo and also achieving statistical significance in an exploratory statistical analysis (p=0.0259).
−Removed: We believe that the maintenance phase data of CALDOSE-1 confirms vidofludimus calcium's activity in the absence of chronic corticosteroid co-administration.
−Removed: Consistent with prior data sets in other patient populations, administration of vidofludimus calcium in the maintenance phase of this trial was observed to be safe and well-tolerated.
+Added: The patent was previously granted to the company in Australia, Canada, Indonesia, Japan and Mexico.
+Added: Publication of Extended Data From Phase 2 EMPhASIS Trial of Vidofludimus Calcium in RRMS in the Peer Reviewed Journal, Neurology ® Neuroimmunology & Neuroinflammation
+Added: On April 30, 2024, we announced that data from our Phase 2 EMPhASIS trial of vidofludimus calcium in patients with RRMS has been published online on April 25, 2024 in Neurology ® Neuroimmunology & Neuroinflammation , an official journal of the American Academy of Neurology.
+Added: The paper, lead authored by coordinating investigator, Robert J.
+Added: Fox, M.D., Staff
+Added: Neurologist, Mellen Center for Multiple Sclerosis, Vice-Chair for Research, Neurological Institute, Cleveland Clinic, Cleveland, Ohio, is entitled, “Safety and Dose-Response of Vidofludimus Calcium in Relapsing Multiple Sclerosis:
+Added: Extended Results of a Placebo-Controlled Phase 2 Trial.”
+Added: Appointment of Jason Tardio as Chief Operating Officer and President and Promotion of Werner Gladdines to Chief Development Officer
+Added: On July 9, 2024, we announced that seasoned biopharmaceutical executive, Jason Tardio, will be joining the company as Chief Operating Officer and President, effective July 12, 2024.
+Added: In the newly created role, Mr.
+Added: Tardio leads internal efforts to prepare for the potential launch of vidofludimus calcium.
+Added: Jason also works closely with Patrick Walsh, Chief Business Officer, to prepare the Company for a range of potential partnership outcomes for vidofludimus calcium, as well as our other drug candidates.
+Added: On July 9, 2024, we also reported that Werner Gladdines, former Vice President, Program Management & Clinical Development Operations, has been promoted to Chief Development Officer.
+Added: In his new role, Mr.
+Added: Gladdines takes over additional strategic and operational responsibility for our overall clinical operations functions.
+Added: Appointment of Simona Skerjanec to Board of Directors
+Added: On July 24, 2024, we announced the appointment of Simona Skerjanec, M.Pharm, MBA, a thought-leader in brain health with decades of experience in drug development and commercialization, as a member of our Board of Directors, effective as of July 22, 2024.
+Added: As a Class I director, Ms.
+Added: Skerjanec’s term lasts until the Company’s 2027 annual meeting of stockholders.
+Added: First Patient Enrolled in Investigator-Sponsored Phase 2 Clinical Trial of Vidofludimus Calcium in Patients with Post COVID Syndrome
+Added: On September 4, 2024, we announced enrollment of the first patient in an investigator-sponsored Phase 2 clinical trial of vidofludimus calcium, entitled, “Randomized Adaptive Assessment of Post COVID Syndrome Treatments_Reducing Inflammatory Activity in Patients with Post COVID Syndrome (RAPID_REVIVE).” The Phase 2 RAPID_REVIVE trial, for which Immunic is providing study medication, is a randomized, placebo-controlled, double-blind, parallel group trial sponsored by the Goethe University Frankfurt, which received trial funding via a grant from the German Federal Ministry of Education and Research.
+Added: Hosted Two Multiple Sclerosis R&D Days in New York City and San Francisco
+Added: At two MS R&D Days, on September 10, 2024 in New York City and on April 9, 2024 in San Francisco, management discussed the latest developments in the MS landscape, along with recent mode of action, preclinical and clinical data supporting the combined neuroprotective, anti-inflammatory and antiviral profile of vidofludimus calcium.
+Added: Presented Key Vidofludimus Calcium Data at the 40th Congress of ECTRIMS, Highlighting Its Therapeutic Potential in Multiple Sclerosis
+Added: On September 18, 2024, we announced the presentation of key data at the 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (“ECTRIMS”), highlighting vidofludimus calcium’s therapeutic potential in MS.
+Added: The data was presented in an oral poster presentation and three ePosters at this conference in Copenhagen, Denmark.
+Added: Positive Outcome of Interim Analysis of Phase 3 ENSURE Program of Vidofludimus Calcium in Relapsing Multiple Sclerosis
+Added: On October 22, 2024, we announced a positive outcome of an interim analysis of our Phase 3 ENSURE program, investigating vidofludimus calcium for the treatment of RMS.
+Added: An unblinded IDMC confirmed that the predetermined futility criteria have not been met and recommended that both ENSURE trials should continue without changes.
+Added: The IDMC considered if a sample size adjustment would be appropriate for either of the two trials based on factors that include statistical analysis and ultimately recommended that the sample sizes for both trials should remain unchanged.
+Added: Announced Publication of Data From Phase 1/1b Clinical Trial of IMU-856 in the Peer Reviewed Journal, The Lancet Gastroenterology & Hepatology
+Added: On November 13, 2024, we announced that the data from our Phase 1/1b clinical trial of IMU-856, has been published in the peer reviewed journal, The Lancet Gastroenterology & Hepatology .
+Added: Lead authored by Dr.
+Added: James Daveson, Gastroenterologist, Wesley Research Institute and Coral Sea Clinical Research Institute, Queensland, Australia, the paper is entitled, “Safety, clinical activity, pharmacodynamics, and pharmacokinetics of IMU-856, a SIRT6 modulator, in coeliac disease:
+Added: a first-in-human, randomised, double-blind, placebo-controlled, phase 1 trial.”
+Added: IMU-856 Demonstrated Dose-Dependent Increase of GLP-1 in Celiac Disease Patients and Corresponding Effects in Preclinical Testing
+Added: On February 20, 2025, we announced that IMU-856 demonstrated a dose-dependent increase of endogenous GLP-1 levels in a post hoc analysis of patients from our Phase 1b clinical trial in celiac disease.
+Added: IMU-856 also showed a dose-dependent reduction of body weight gain and food consumption in preclinical in vivo testing.
+Added: These effects may indicate the potential for IMU-856 as an oral treatment option for weight management.
+Added: The post hoc analysis of our Phase 1b clinical trial of IMU-856 in celiac disease patients measured blood concentrations of GLP-1, between baseline and day 28, in a fasting state.
+Added: A highly statistically significant (day 29:
+Added: 80 mg p=0.014;
+Added: 160 mg p=0.003) and dose-dependent increase of GLP-1 versus placebo control was detectable, even in the small patient population in this Phase 1b clinical trial (baseline:
+Added: N placebo = 11, N 80 mg IMU-856 = 13, N 160 mg IMU-856 = 13).
+Added: These clinical findings were corroborated by effects observed in a 6-month preclinical in vivo study, where IMU-856 was found to reduce body weight gain accompanied by food consumption in a dose-dependent fashion up to -40 %, compared to the control group, which was found to be linked to reduced food intake.
Product Acquisition History
−Removed: Our wholly-owned subsidiary Immunic AG acquired vidofludimus calcium and izumerogant in September 2016 through asset acquisitions from 4SC AG (hereinafter, “4SC”), a publicly traded company based in Planegg-Martinsried, Germany.
+Added: Our wholly-owned German subsidiary Immunic AG acquired vidofludimus calcium and izumerogant in September 2016 through asset acquisitions from 4SC AG (hereinafter, “4SC”), a publicly traded company based in Planegg-Martinsried, Germany.
On March 31, 2021, Immunic AG and 4SC entered into a Settlement Agreement, pursuant to which Immunic AG settled its remaining obligation of a 4.4% royalty on net sales for $17.25 million.
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We are led by a team of dedicated and committed experienced professionals with an entrepreneurial spirit and track record of successful licensing transactions in the healthcare industry, worldwide.
−Removed: The team brings together several decades of leadership experience in the pharmaceutical industry with a strong scientific background and sound knowledge in drug
−Removed: discovery, product development, chemistry, manufacturing and controls processes, intellectual property, clinical trial design, health economics and market access, merger and acquisitions, capital markets, corporate finance, business development, regulatory affairs and project valuation.
+Added: The team brings together several decades of leadership experience in the pharmaceutical industry with a strong scientific background and sound knowledge in drug discovery, product development, chemistry, manufacturing and controls processes, intellectual property, clinical trial design, health economics and market access, merger and acquisitions, capital markets, corporate finance, business development, regulatory affairs and project valuation.
Our team members are inventors on project-related patents and have successfully published project-related scientific publications.
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Vidofludimus calcium is a small molecule investigational drug in development as an oral next-generation treatment option for patients with MS and other chronic inflammatory and autoimmune diseases.
−Removed: If approved, we believe that vidofludimus calcium, with combined neuroprotective, anti-inflammatory, and antiviral effects, has the potential to be a unique treatment option targeted to the complex pathophysiology of MS.
−Removed: Preclinical data showed that vidofludimus calcium activates the neuroprotective transcription factor nuclear receptor related 1 (“Nurr1”), which is associated with direct neuroprotective properties and may enhance the potential benefit for patients.
+Added: If approved, we believe that vidofludimus calcium, with combined neuroprotective, anti-inflammatory, and antiviral effects as well as a favorable safety and tolerability profile, has the potential to be a unique treatment option targeted to the complex pathophysiology of MS.
+Added: Preclinical data showed that vidofludimus calcium activates the neuroprotective transcription factor Nurr1, which is associated with direct neuroprotective properties and may enhance the potential benefit for patients.
Nurr1 activation mediates its neuroprotective function by acting in microglia, astrocytes and neurons.
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Therefore, activation of Nurr1 by vidofludimus calcium may halt neurodegeneration and disability progression in patients suffering from MS and other degenerative diseases.
−Removed: Additionally, vidofludimus calcium is a known inhibitor of the enzyme dihydroorotate dehydrogenase (“DHODH”), which is a key enzyme in the metabolism of overactive immune cells and virus-infected cells.
+Added: Additionally, vidofludimus calcium is a known inhibitor of the enzyme DHODH, which is a key enzyme in the metabolism of overactive immune cells and virus-infected cells.
This mechanism is associated with the anti-inflammatory and antiviral effects of vidofludimus calcium.
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Treatment with vidofludimus calcium may avoid virus infections and reactivations, one of the major drawbacks of the long-term use of traditional immunomodulators.
−Removed: In addition, the blockage of reactivation of EBV could be of highest importance for MS patients, as infection with and reactivation of EBV was brought into connection with disease onset and progression (Bjornevik et al.
−Removed: 2022/Lanz et al., 2022/Schneider-Hohendorf et al.
−Removed: Efficacy of vidofludimus has been observed in several animal disease models for IBD, MS, as well as systemic lupus erythematosus and transplant rejection.
+Added: In addition, the blockage of reactivation of EBV could be of highest importance for MS patients, as infection with and reactivation of EBV was brought into connection with disease onset and progression (Bjornevik et al., 2022/Lanz et al., 2022/Schneider-Hohendorf et al., 2022).
+Added: Efficacy of vidofludimus has been observed in several animal disease models for MS, IBD, as well as systemic lupus erythematosus and transplant rejection.
Previous filings by us with the SEC have summarized the development history of vidofludimus and the previous amorphous formulation of the free acid form of vidofludimus.
−Removed: After the consummation of the asset acquisition from 4SC, we developed and filed a patent application for a new specific polymorph of the calcium salt formulation of vidofludimus, vidofludimus calcium, which we believe exhibits improved physicochemical and pharmacokinetic (“PK”) properties.
+Added: After the consummation of the asset acquisition from 4SC, we developed and filed several new patent applications for a new specific polymorph of the calcium salt formulation of vidofludimus, vidofludimus calcium, which we believe exhibits improved physicochemical and pharmacokinetic (“PK”) properties.
In 2017, we completed two Phase 1 studies of single or repeated once-daily doses of vidofludimus calcium in healthy human subjects, where we observed results supporting tolerability of repeated daily dosing of up to 50 mg of vidofludimus calcium.
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SPMS is identified following an initial relapsing-remitting course, after which the disease becomes more steadily progressive, with or without other disease activity present.
+Added: Active SPMS, the progressive disease form where relapses and MRI lesions are still present, is generally counted to the RMS spectrum.
+Added: The forms of SPMS that are considered part of the PMS spectrum are non-active SPMS (where disability worsening occurs despite no relapses observed in the last 24 months and no MRI lesions present in the last 12 months) or non-relapsing SPMS (where no relapses occurred in the last 24 months, but MRI lesions may be present at any time).
MS is a disease with unpredictable symptoms that can vary widely.
Common early signs of MS include vision problems, tingling and numbness or other unspecific neurological symptoms.
−Removed: Diagnosis of MS is confirmed via blood tests and a spinal tap, in which a small sample of fluid is removed from the spinal cord.
−Removed: However, most important for diagnosis are characteristic CNS lesions found using MRI.
+Added: Diagnosis of MS can be confirmed via blood tests and a spinal tap, in which a small sample of fluid is removed from the spinal cord.
+Added: However, most important for diagnosis are characteristic CNS lesions detected by MRI.
According to the National Multiple Sclerosis Society (2019), there are nearly one million patients in the United States living with MS.
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The disease has a large economic impact as it affects mainly young adults in the prime working age, peaking around 30 years old, although MS can occur in children and in adults.
−Removed: MS is up to three times more common in women than in men.
+Added: MS is up to three times more common in women than in men (Green J, Dunn WH 2012) .
MS affects twice as many women and men in certain age cohorts and is more common in areas inhabited by people of northern European ancestry, such as Europe, the United States, Canada, New Zealand and parts of Australia.
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However, the study also found that approximately half of the disability accumulating in RMS patients were not related to relapse activity.
−Removed: This suggests that other mechanisms including PIRA already contribute half of the disability to disease progression in RMS.
−Removed: In addition, this investigation found that many currently available drugs were able to delay or avoid disability associated with relapse activity but was unable to diminish the impact of PIRA.
+Added: This suggests that other mechanisms including PIRA already contribute half of the disability to disease progression in RMS – already from early stages of the disease.
+Added: In addition, this investigation found that currently available drugs were able to delay or avoid disability associated with relapse activity but were unable to diminish the impact of PIRA.
This confirms that PIRA presumably is caused by a process that is not addressed by currently used anti-inflammatory medications which predominantly address focal inflammation in MS.
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Bjornevik et al.
−Removed: (2022) shed new light on the role of EBV infection previously postulated to trigger MS.
+Added: (2022) shed additional light on the role of EBV infection previously postulated to trigger MS.
They analyzed EBV antibodies in serum from 801 individuals who developed MS among a cohort of more than 10 million people active in the US military over a 20-year period (1993 to 2013).
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These findings cannot be explained by any known risk factor for MS and suggest EBV as the leading cause of MS.
−Removed: In addition, antibody producing cells directed against the latent EBV protein EBNA1 were found in the CSF of MS patients.
+Added: In addition, antibody producing cells directed against the latent EBV protein EBNA1 were found in the cerebrospinal fluid of MS patients.
Cross reactivity of anti-EBNA1 antibodies against GlialCAM, a protein that is predominantly expressed in glial cells in the CNS and potentially important in the myelination process of axons, further corroborates the connection between EBV infections and pathologic processes in MS (Lanz et al., 2022).
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The study found that EBV-related antigens were on top of the list of antigens seen by T cells in MS patients but not in other EBV-infected populations.
−Removed: These results suggest that ongoing EBV reactivation seems to be an ongoing trigger for the immune system in MS patients and may be the trigger for disease progression and ongoing neurogenerative processes.
+Added: These results suggest that ongoing EBV reactivation seems to be an ongoing trigger for the immune system in MS patients and may be the trigger for disease progression and ongoing neurodegenerative processes.
Current Treatment Options
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We intend to develop vidofludimus calcium as a disease-modifying therapy for RMS.
−Removed: The initial treatment options for RMS patients are often beta interferons (either as interferon beta-1a or interferon beta-1b) or glatiramer acetate, all of which are given by injection.
−Removed: For patients requiring more advanced treatment options, there are several oral medications, such as dimethyl fumarate, fingolimod, siponimod, ponesimod, teriflunomide, ozanimod or cladribine, and biologics, such as natalizumab, ocrelizumab, ublituximab, ofatumumab or alemtuzumab, approved for commercial use in MS in various countries.
−Removed: In addition, some of these drugs already have generic versions available in some countries and other drugs will become generic in the next years.
+Added: Historically, the initial treatment options for RMS patients are often beta interferons (either as interferon beta-1a or interferon beta-1b) or glatiramer acetate, all of which are given by injection.
+Added: In addition, there are several oral medications, such as dimethyl fumarate, fingolimod, siponimod, ponesimod, teriflunomide, ozanimod or cladribine, and biologics, such as natalizumab, ocrelizumab, ublituximab, ofatumumab or alemtuzumab, approved for commercial use in MS in various countries.
+Added: All of these medications are commonly used across the spectrum of patients with RMS.
+Added: Some of these drugs have generic versions available in some countries and other drugs will become generic in the next years.
With regard to PMS, there is currently only one drug approved:
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Other available medications in MS have previously been tested in different forms of PMS, such as siponimod in the Phase 3 EXPAND trial in SPMS patients.
−Removed: Although the study found a statistical significant effect in active SPMS patients, the treatment for non-active SPMS patients remained elusive.
+Added: Although the study found a statistically significant effect in active SPMS patients, the treatment for non-active SPMS patients remained elusive.
It also highlighted the fact that currently available anti-inflammatory treatments in RMS may in general have no utility in non-active SPMS as the disease progress may be predominantly driven by “smoldering disease” rather than focal inflammation.
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No case of PML has yet been reported for the DHODH inhibitor teriflunomide, which has been one of the key differentiators of teriflunomide from other disease-modifying therapies in RMS.
−Removed: The active moiety of vidofludimus calcium has also shown direct antiviral effects in several models of virus-infected cells, which we believe is caused by DHODH inhibition.
+Added: The active moiety of vidofludimus calcium has also shown direct antiviral effects in multiple models of virus-infected cells, which we believe is caused by DHODH inhibition.
+Added: Of specific interest, vidofludimus calcium reduces the reactivation of EBV in a dose dependent fashion which was demonstrated in latently EBV-infected cell models.
Subject to further clinical trials, we believe that could be an important potential differentiator against other drug classes in RMS.
Current Development Plan and Clinical Studies
−Removed: Depending on the results of our ongoing clinical trials, we believe that vidofludimus calcium has the potential to demonstrate medically important advantages versus other treatments, due to its safety profile as well as its neuroprotective, anti-inflammatory, and anti-viral effects observed-to-date.
+Added: Depending on the results of our ongoing clinical trials, we believe that vidofludimus calcium has the potential to demonstrate medically important advantages versus other treatments, due to its safety and tolerability profile as well as its neuroprotective, anti-inflammatory, and anti-viral effects observed, to date.
Vidofludimus calcium could provide MS patients with a distinctive therapy that is uniquely matched to the biological drivers of MS.
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Our Phase 2 EMPhASIS trial of vidofludimus calcium in RRMS consisted of two cohorts:
−Removed: The full data set of Cohort 1, which evaluated efficacy and safety of 30 mg or 45 mg once daily vidofludimus calcium compared to placebo, was published by us in August and September 2020, respectively.
+Added: The full data set of Cohort 1, which evaluated efficacy and safety of 30 mg or 45 mg once daily vidofludimus calcium compared to placebo, was published in August and September 2020, respectively.
The Cohort 1 results were subsequently published in the peer reviewed journal, Annals of Clinical and Translational Neurology (Fox et al., 2022).
−Removed: The results of Cohort 2, which evaluated efficacy and safety of 10 mg once daily vidofludimus calcium compared to placebo, were also published by us.
+Added: The results of Cohort 2, which evaluated efficacy and safety of 10 mg once daily vidofludimus calcium compared to placebo, were published in February 2022.
+Added: The combined Cohort 1 and 2 results were published in the peer reviewed journal, Neurology ® Neuroimmunology & Neuroinflammation , an official journal of the American Academy of Neurology (Fox et al., 2024).
On August 2, 2020, we announced positive top-line data from our Phase 2 EMPhASIS trial of vidofludimus calcium in patients with RRMS.
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We concluded from this data, along with previously published data from Cohort 1, that 30 mg once daily vidofludimus calcium is the most appropriate anti-inflammatory dose for Phase 3 clinical trials in patients with RMS.
−Removed: Final data from Cohort 2 showed that the anti-inflammatory effects of vidofludimus calcium at the 10 mg dose were observed to be lower (13% reduction of gadolinium-enhancing MRI lesions up to 24 weeks, as compared to placebo) than those found with the 30 mg vidofludimus calcium dose in the pooled Cohort 1 and 2 data (78% reduction), providing further support for the selection of 30 mg dosing in the ongoing ENSURE trials in RMS.
+Added: On February 24, 2022, we published final data from Cohort 2 showing that the anti-inflammatory effects of vidofludimus calcium at the 10 mg dose were observed to be lower (13% reduction of gadolinium-enhancing MRI lesions up to 24 weeks, as compared to placebo) than those found with the 30 mg vidofludimus calcium dose in the pooled Cohort 1 and 2 data (78% reduction), providing further support for the selection of 30 mg dosing in the ongoing ENSURE trials in RMS.
Final Cohort 2 data also provided evidence of dose-proportional neuroprotective activity.
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Taken together, these last two observations suggest that higher doses, such as 45 mg vidofludimus calcium, may be preferred doses for clinical trials in which neuroprotective effects are the main mechanism for improvement, such as in PMS.
−Removed: While Cohort 1 blinded treatment was completed right before the COVID-19 pandemic started, final Cohort 2 data provide additional evidence that ongoing vidofludimus calcium treatment may reduce the risk of COVID-19 infections, presumably related to its known antiviral activity.
+Added: While Cohort 1 blinded treatment was completed right before the coronavirus disease 2019 (“COVID-19”) pandemic, final Cohort 2 data provided additional evidence that ongoing vidofludimus calcium treatment may reduce the risk of COVID-19 infections, presumably related to its known antiviral activity.
In the entire Cohort 2 population of 59 patients, who were enrolled during pandemic conditions, incidental COVID-19 infections in the active treatment group were less frequent (8.5%, n=4/47) than in the placebo group (25.0%, n=3/12).
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We believe that this finding suggests that vidofludimus calcium may be able to act directly within the CNS.
−Removed: On November 17, 2022, we reported newly available data from the EMPhASIS trial.
−Removed: The trial includes an optional long-term OLE phase running up to 9.5 years.
+Added: On November 17, 2022, we reported additional data from the EMPhASIS trial.
+Added: The trial includes an optional long-term open-label extension (“OLE”) phase running up to 9.5 years.
An interim analysis was performed with data extraction in October 2022, when 209 patients remained on treatment in the OLE phase, some of whom have already received more than 180 continuous weeks (approximately four years) of active treatment with vidofludimus calcium.
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The OLE phase also showed low relapse activity.
+Added: As of January 2025, more than 180 patients still remained in the OLE phase of the EMPhASIS trial, with more than five total treatment years.
Further information regarding our EMPhASIS trial in RRMS can be found on ClinicalTrials.gov under the identifier NCT03846219.
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The ENSURE program comprises two identical multicenter, randomized, double-blind Phase 3 clinical trials designed to evaluate the efficacy, safety, and tolerability of vidofludimus calcium versus placebo in RMS patients.
−Removed: Based on vidofludimus calcium’s highly significant activity in preventing lesion formation in our Phase 2 EMPhASIS trial in RMS, the strong and consistent correlation observed between lesion formation and clinical relapse in third-party clinical trials, and the drug’s robust safety profile, to date, we believe that this Phase 3 program should provide a straightforward path towards potential regulatory approval of vidofludimus calcium in RMS.
+Added: Based on vidofludimus calcium’s highly significant activity in preventing lesion formation in our Phase 2 EMPhASIS trial in RRMS, the strong and consistent correlation observed between lesion formation and clinical relapse in third-party clinical trials, and the drug’s robust safety profile, to date, we believe that this Phase 3 program should provide a straightforward path towards potential regulatory approval of vidofludimus calcium in RMS.
Each of the identical twin Phase 3 clinical trials, titled ENSURE-1 and ENSURE-2, is expected to enroll approximately 1,050 adult patients with active RMS at more than 100 sites in more than 15 countries, including the United States, India and countries in Latin America, Central and Eastern Europe.
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The first patient in ENSURE-2 was enrolled in January 2022.
−Removed: A non-binding interim futility analysis to assess event rates is planned to occur after approximately half of the relapse events have occurred in the double-blind treatment periods.
−Removed: This analysis is intended to inform potential sample size adjustment and help ensure that final study readout is not planned to occur before sufficient events have been achieved.
−Removed: We currently expect to report data from the interim analysis of the ENSURE program in late 2024 and to read-out the first of the ENSURE trials in the second quarter of 2026.
+Added: Completion of the first of the ENSURE trials is currently anticipated in the second quarter of 2026;
+Added: and the second ENSURE trial in the second half of 2026.
+Added: On October 22, 2024, we announced a positive outcome of an interim analysis of our Phase 3 ENSURE program.
+Added: An unblinded IDMC confirmed that the predetermined futility criteria have not been met and recommended that both ENSURE trials should continue without changes.
+Added: The IDMC considered if a sample size adjustment would be appropriate for either of the two trials based on factors that include statistical analysis and ultimately recommended that the sample sizes for both trials should remain unchanged.
Further information regarding our ENSURE program in RMS can be found on ClinicalTrials.gov under the identifiers NCT05134441 (ENSURE-1) and NCT05201638 (ENSURE-2), respectively.
−Removed: The execution of Phase 3 clinical trials usually requires the use of a commercial formulation of the investigational drug manufactured at commercially usable quantities.
−Removed: Manufactures under contract with us have developed and produced a formulation of vidofludimus calcium which would allow commercially usable production batches.
−Removed: A Phase 1 bioequivalence study between the previous and the new formulation of vidofludimus calcium was completed and showed bioequivalence regarding drug exposure curve in blood plasma (area under the curve).
−Removed: A confirmatory relative bioavailability and food effect study demonstrated a high bioavailability of tablets as compared to a drinking solution and confirmed the in vitro finding of a complete and fast dissolution profile in human subjects.
−Removed: No food effect on the uptake or elimination of vidofludimus calcium after administration of the tablets was observed.
−Removed: Additional investigations regarding metabolite characterization, metabolic modeling and potential drug-drug interactions, as well as other activities relating to clinical pharmacology are either ongoing or planned in anticipation for presentation to regulatory authorities.
−Removed: Discussions on a pediatric development plan in pediatric-onset MS have been initiated with the FDA , based on a proposal developed with clinical and regulatory advisors.
Phase 2 Clinical Trial of Vidofludimus Calcium in PMS (CALLIPER Trial)
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Our current expectation is to read-out top-line data of the CALLIPER trial in April 2025.
+Added: The Phase 2 CALLIPER trial is focused on progressive forms of MS.
+Added: Its key objective is to corroborate vidofludimus calcium’s neuroprotective potential, as exemplified by slowing of brain atrophy and delay in disability worsening, in this patient population where focal inflammatory disease no longer dominates.
+Added: The second objective is to determine whether there is sufficient evidence of efficacy and safety to warrant a confirmatory Phase 3 program in one or more of the PMS subtypes.
+Added: Additional clinical studies and the potential regulatory path forward specific to the treatment of PMS will be informed by the results of the CALLIPER trial and will be further assessed accordingly.
+Added: Moreover, neurodegeneration is a key concern in both PMS and RMS, since axonal and neural damage is responsible for the increasing and often severe disability experienced by patients.
+Added: Therefore, we believe that, if the CALLIPER trial is successful in showing a beneficial effect of vidofludimus calcium, this data, along with the ENSURE program and vidofludimus calcium’s strong safety and tolerability profile, may allow for a meaningful clinical differentiation of vidofludimus calcium from other MS medications and potentially attractive commercial positioning.
+Added: However, we do not believe that data from the CALLIPER trial are a pre-condition for filing an NDA in RMS.
The multicenter, randomized, double-blind, placebo-controlled Phase 2 CALLIPER trial of vidofludimus calcium enrolled 467 patients with primary PMS, or active or non-active secondary PMS at more than 70 sites in North America, Western, Central and Eastern Europe.
Patients were randomized to either 45 mg daily doses of vidofludimus calcium or placebo in a double-blinded fashion.
−Removed: The trial’s primary endpoint is the annualized rate of percent brain volume change up to 120 weeks.
−Removed: Key secondary endpoints include the annualized rate of change in whole brain atrophy and time to 24-week confirmed disability progression based on EDSS which may further support disability data from the ENSURE trials.
+Added: The trial’s primary endpoint is the annualized rate of percent brain volume change (“PBVC”) up to 120 weeks.
+Added: The key secondary endpoint is time to 24-week confirmed composite disability progression based on EDSS, timed 25-foot walk and 9-hole peg test, which may further support disability data from the ENSURE trials.
On October 9, 2023, we announced positive interim data from our Phase 2 CALLIPER trial of vidofludimus calcium in patients with PMS.
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We believe that the interim data showed biomarker evidence that vidofludimus calcium's activity extends beyond the previously observed anti-inflammatory effects, thereby further reinforcing its neuroprotective potential.
−Removed: Serum NfL responses were consistently observed for vidofludimus calcium across progressive MS disease and all subpopulations.
−Removed: In the overall PMS population at 24 weeks (N=203), vidofludimus calcium was associated with a 6.7% reduction from baseline in serum NfL, compared to a 15.8% increase over baseline in placebo (p=0.01, post hoc).
−Removed: At 48 weeks (N=79), vidofludimus calcium reduced serum NfL by 10.4% from baseline, compared to a 6.4% increase in placebo.
−Removed: Substantial reductions were also seen across all PMS subtypes, as well as in patients that show or do not show disease and/or MRI activity.
−Removed: Although early, interim GFAP data also showed a promising signal:
−Removed: at 24 weeks (N=203), GFAP increased by 3.7% for vidofludimus calcium, and 4.4% for placebo.
−Removed: At 48 weeks (N=79), the change was only 2.7% for vidofludimus calcium, with a 6.4% increase for placebo.
−Removed: Progression of GFAP response is generally thought to evolve more slowly than NfL, and we believe that a longer follow-up may further strengthen this signal.
−Removed: The Phase 2 CALLIPER trial is intended to run concurrently with and to complement the Phase 3 program in RMS.
−Removed: In particular, CALLIPER is focused on progressive forms of MS and is designed to corroborate vidofludimus calcium’s neuroprotective potential, as exemplified by slowing of brain atrophy and delay in disability worsening.
−Removed: Neurodegeneration is a key concern in both PMS and RMS, since axonal and neural damage is responsible for the increasing and often severe disability experienced by patients.
−Removed: We believe that, if the CALLIPER trial is successful in showing a beneficial effect of vidofludimus calcium, this data, along with the ENSURE program and vidofludimus calcium’s strong safety and tolerability profile, may allow for a meaningful clinical differentiation of vidofludimus calcium from other MS medications and potentially attractive commercial positioning.
−Removed: Although a supportive trial, we do not believe that data from the CALLIPER trial are a pre-condition for filing an NDA in RMS.
−Removed: Additional clinical studies and the potential regulatory path forward specific to the treatment of PMS will be informed by the results of the CALLIPER trial and will be further assessed accordingly.
+Added: As of January 2025, more than 380 patients are treated in the OLE phase of the CALLIPER trial.
Further information regarding our CALLIPER trial in PMS can be found on ClinicalTrials.gov under the identifier NCT05054140.
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The trial did not achieve the primary endpoint of clinical remission for the pooled 30 and 45 mg/day active dose groups of vidofludimus calcium versus placebo at week 10.
−Removed: In addition, no meaningful differences were observed between the three active dose groups for the overall intent-to-treat patient population (10 mg/day:
−Removed: 14.9%, 30 mg/day:
−Removed: 10.6%, 45 mg/day:
−Removed: 13.6%, placebo:
−Removed: 12.5%) or for the trial’s other secondary endpoints, including symptomatic remission, or endoscopic healing.
+Added: In addition, no meaningful differences were observed between the three active dose groups for the overall intent-to-treat patient population or for the trial’s other secondary endpoints, including symptomatic remission, or endoscopic healing.
Consistent with prior data sets in other patient populations, administration of vidofludimus calcium in this clinical trial was observed to be safe and well-tolerated.
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Consistent with prior data sets in other patient populations, administration of vidofludimus calcium in the maintenance phase of this trial was observed to be safe and well-tolerated.
+Added: The results of the CALDOSE-1 trial were published in the peer reviewed journal, Clinical and Translational Gastroenterology (D’Haens et al., 2025).
Further information regarding our CALDOSE-1 trial in UC can be found on ClinicalTrials.gov under the identifier NCT03341962.
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Moreover, an agreement for a pediatric development plan (“PSP”) is required to be achieved with the FDA prior to NDA submission.
+Added: Such PSP agreements have been reached with the FDA, who waived Immunic’s requirement to conduct clinical studies in pediatric patients for both RMS and PMS.
Future human clinical testing and marketing outside the United States will be subject to foreign regulatory requirements.
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In many countries outside of the United States, coverage, pricing and reimbursement approvals are also required.
−Removed: We have an ongoing Phase 3 program for vidofludimus calcium in RMS and an ongoing Phase 2 clinical trial for vidofludimus calcium in PMS.
+Added: We have an ongoing Phase 3 clinical program for vidofludimus calcium in RMS and an ongoing Phase 2 clinical trial for vidofludimus calcium in PMS.
For our most advanced indication RMS, marketing approval requires completion of two successful, well-controlled Phase 3 clinical trials.
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Our existing API manufacturer has the capacity for manufacturing of up to metric tons.
+Added: The execution of Phase 3 clinical trials usually requires the use of a commercial formulation of the investigational drug manufactured at commercially usable quantities.
+Added: Manufactures under contract with us have developed and produced a formulation of vidofludimus calcium which would allow commercially usable production batches.
+Added: A Phase 1 bioequivalence study between the previous and the new formulation of vidofludimus calcium was completed and showed bioequivalence regarding drug exposure curve in blood plasma (area under the curve).
+Added: A confirmatory relative bioavailability and food effect study demonstrated a high bioavailability of tablets as compared to a drinking solution and confirmed the in vitro finding of a complete and fast dissolution profile in human subjects.
+Added: No food effect on the uptake or elimination of vidofludimus calcium after administration of the tablets was observed.
+Added: Additional investigations regarding metabolite characterization, metabolic modeling and potential drug-drug interactions, as well as other activities relating to clinical pharmacology are either completed, ongoing or planned in anticipation for presentation to regulatory authorities.
Vidofludimus Calcium Intellectual Property, Licenses and Royalties
Vidofludimus calcium is covered by several layers of granted patents in the United States, Europe and other jurisdictions around the world.
−Removed: These patents are directed towards composition-of-matter for salt forms of vidofludimus, including the specific calcium salt form used in Immunic’s clinical trials;
−Removed: the treatment of RMS with a specific dose strength used in the clinical trials;
−Removed: as well as the dosing regimens, including those used in clinical trials for the treatment of MS.
+Added: These patents are directed towards composition-of-matter for salt forms of vidofludimus, including the
+Added: specific calcium salt form used in Immunic’s clinical trials;
+Added: the treatment of RRMS with a specific dose strength used in the clinical trials;
+Added: the dosing regimens, including those used in clinical trials for the treatment of MS, as well as composition-of-matter of a specific polymorph of vidofludimus calcium and a related method of production of the material.
In the United States, these patents provide protection into 2041, unless extended further.
−Removed: In addition, pending applications are directed towards composition-of-matter of a specific polymorph of vidofludimus calcium and a related method of production of the material;
−Removed: as well as the use of vidofludimus calcium and other salt forms as well as free acid forms for treating neurodegenerative diseases.
−Removed: If granted, these applications could provide protection up to 2044, unless extended further.
+Added: In addition, a pending application is directed towards the use of vidofludimus calcium and other salt forms as well as free acid forms for treating neurodegenerative diseases.
+Added: If granted, this application could provide protection up to 2044, unless extended further.
+Added: An additional patent, covering the treatment of long COVID, has been granted in the US and in Europe, also providing protection until 2041.
Finally, further undisclosed patent applications dedicated to strengthening the exclusivity period are currently in process.
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IMU-856 is an orally available and systemically acting small molecule modulator that targets Sirtuin 6 (“SIRT6”), a protein which serves as a transcriptional regulator of intestinal barrier function and regeneration of bowel epithelium.
−Removed: Based on preclinical data, we believe this compound may represent a unique treatment approach, as the mechanism of action targets the restoration of the intestinal barrier function and bowel wall architecture in patients suffering from gastrointestinal diseases such as celiac disease, IBD, short bowel syndrome, irritable bowel syndrome with diarrhea and other intestinal barrier function associated diseases.
+Added: Based on preclinical data, we believe this compound may represent a unique treatment approach, as the mechanism of action targets the restoration of the intestinal barrier function and bowel wall architecture in patients suffering from gastrointestinal diseases such as celiac disease, IBD, GvHD, irritable bowel syndrome with diarrhea and other intestinal barrier function associated diseases.
We believe that, because IMU-856 has been shown in preclinical investigations to avoid suppression of immune cells, it may therefore have the potential to maintain immune surveillance for patients during therapy, which would be an important advantage versus immunosuppressive medications.
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To date, there are no adequate treatment strategies to ameliorate impaired barrier function.
+Added: IMU-856 has also shown potential as an oral treatment option for weight management, by increasing endogenous GLP-1 levels in patients and reducing body weight gain and food consumption in preclinical in vivo testing.
Celiac Disease
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Celiac disease is estimated to affect 1 in 100 people worldwide (Celiac Disease Foundation, 2022).
−Removed: In the United States, alone, it is estimated that there are approximately two million people diagnosed with celiac disease and an additional approximately one million people are undiagnosed, yet still at risk for long-term health complications.
+Added: In the United States, alone, it is estimated that there are approximately two million people diagnosed with celiac disease (Singh et al., 2018) and an additional approximately one million people are undiagnosed, yet still at risk for long-term health complications (Choung et al., 2016).
Ongoing inflammation in patients with celiac disease can cause debilitating symptoms and serious medical complications.
1 unchanged sentence
Small bowel damage often leads to nutrient malabsorption that can result in a range of further clinical manifestations such as fatigue, anemia, osteopenia, weight loss, or failure to thrive in children.
−Removed: In addition, extra-intestinal symptoms and systemic manifestations are often present, such as dermatitis herpetiformis, infertility, or neurological
−Removed: and skeletal disorders.
+Added: In addition, extra-intestinal symptoms and systemic manifestations are often present, such as dermatitis herpetiformis, infertility, or neurological and skeletal disorders.
Patients with persistent villous atrophy show an increased risk of lymphoproliferative malignancy.
The intestinal epithelial barrier, physiologically impermeable to macromolecules such as gliadin, is recognized to play an important role in the pathogenesis of celiac disease.
+Added: In children, nutrient malabsorption can affect growth and development, in addition to causing the symptoms seen in adults.
Current Treatment Options
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However, a significant number of patients continue to experience disease activity and persistent symptoms despite a gluten-free diet as gluten is present in numerous food products, medications, household products and cosmetics as impurity.
−Removed: Thus, there is an increasing number of different treatment options in clinical development to reduce the burden of living with celiac disease and improve long-term health outcomes.
+Added: Thus, there is an increasing number of different treatment options in clinical development to reduce the burden of living with celiac disease and improve long-term health outcomes (Buriánek, Gege, Marinković, 2024).
+Added: Treatment goals include resolution of bowel inflammation and relief of associated clinical signs and symptoms.
+Added: This is underlined by the recently published FDA Draft Guidance (April 2022) for the development of drugs for the adjunctive treatment of gluten-free diet.
Current Development Plan and Clinical Studies
−Removed: Current treatments of many conditions of the bowel are aimed at inhibiting inflammation, but they do not target the impaired bowel wall barrier function.
−Removed: IMU-856 is designed to target pathways impacting the bowel wall barrier function and is aimed to normalize such function.
+Added: Current treatments of many conditions of the bowel are designed to inhibit inflammation, but they do not target the impaired bowel wall barrier function.
+Added: IMU-856 is designed to target pathways impacting the bowel wall barrier function and aims to normalize such function.
We believe that normalized bowel wall barrier function may avoid antigen triggers, which may lead to the achievement and maintenance of remission without significantly influencing the immune competency of the patient.
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Celiac Disease Patients
−Removed: The third portion of the Phase 1 clinical trial of IMU-856 was structured as a double-blind, randomized, placebo-controlled Phase 1b trial, designed to assess the safety and tolerability of IMU-856 in patients with celiac disease during periods of gluten-
−Removed: free diet and a 15-day gluten challenge with 6 g gluten given daily.
−Removed: The trial was conducted at sites in Australia and New Zealand.
+Added: The third portion of the Phase 1 clinical trial of IMU-856 was structured as a double-blind, randomized, placebo-controlled Phase 1b trial, designed to assess the safety and tolerability of IMU-856 in patients with celiac disease during periods of gluten-free diet and a 15-day gluten challenge with 6 g gluten given daily.
+Added: The trial was conducted at sites in Australia and New
A total of 43 patients were enrolled in two consecutive cohorts with 80 mg or 160 mg of IMU-856 or placebo given once-daily over 28 days.
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IMU-856 was also observed to be safe and well-tolerated in this trial.
−Removed: There were no IMP-related serious or severe treatment-emergent adverse events nor was there any dose-dependency in adverse events.
+Added: There were no IMP-related serious or severe treatment-emergent adverse events or any dose-dependency in adverse events.
Moreover, the rates of treatment-emergent adverse events in non-disease-related parameters were comparable between the active treatment groups and placebo.
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Most importantly, the observed protection of intestinal villi from gluten-induced destruction, independent of targeting immune mechanisms involved specifically in celiac disease, appears to be unique among proposed therapeutic approaches and may be applicable to other gastrointestinal diseases such as IBD, short bowel syndrome and irritable bowel syndrome with diarrhea.
−Removed: We are currently preparing clinical Phase 2 testing of IMU-856 in patients with OACD despite gluten-free diet, while also considering further potential clinical applications in other gastrointestinal disorders.
+Added: Contingent on financing, licensing or partnering, we are currently preparing clinical Phase 2 testing of IMU-856 in patients with OACD despite gluten-free diet, while also considering further potential clinical applications in other gastrointestinal disorders.
IMU-856 Manufacturing and Formulation
12 unchanged sentences
Going forward, Daiichi Sankyo is eligible to receive future development, regulatory and sales milestone payments, as well as royalties related to IMU-856.
−Removed: On August 16, 2022, we announced that we have received a Notice of Allowance from the USPTO for patent application 16/646130, entitled, “Compound Having Cyclic Structure.” The patent covers composition-of-matter of IMU-856 and related pharmaceutical compositions and is expected to provide protection into at least 2038, without accounting for potential PTE.
+Added: A patent application covering composition-of-matter of IMU-856 and related pharmaceutical compositions has been granted in the US and other jurisdictions and is expected to provide protection into at least 2038, without accounting for potential patent term extension.
+Added: In addition, a pending application is directed towards the treatment of inflammatory/gastrointestinal diseases (e.g., celiac disease) with IMU-856.
+Added: Further undisclosed patent applications dedicated to other diseases are currently in processing.
We have selected IMU-381 as a development candidate to specifically address the needs of gastrointestinal diseases.
3 unchanged sentences
In the United States, the FDA regulates drugs under the federal Food, Drug, and Cosmetic Act (“FDCA”), and its implementing regulations.
−Removed: All of Immunic’s drug development candidates require approval from the FDA (for the United States), EMA (for the European Union) and other national competent authorities (for any other territory) before they can be marketed for sale in the applicable jurisdiction.
+Added: All of Immunic’s drug development candidates require approval from the FDA (for the United States), EMA (for the European Union) and/or other national competent authorities (for any other territory) before they can be
+Added: marketed for sale in the applicable jurisdiction.
The activities required before drugs or biologics may be marketed in the United States include:
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The data assessed by the FDA in reviewing an NDA includes preclinical testing data, including animal data, CMC data, PK, PD and drug-drug interaction data, as well as human clinical safety and efficacy data.
−Removed: Moreover, an agreement for a pediatric development plan (“PSP”) is required to be achieved with the FDA prior to NDA submission.
+Added: Moreover, an agreement for a PSP is required to be achieved with the FDA prior to NDA submission.
Preclinical tests include laboratory evaluations of product chemistry, toxicity and formulation, as well as animal studies.
48 unchanged sentences
Human Capital
−Removed: As of February 1, 2024, we had 77 employees, eight of whom held M.D.
+Added: As of March 1, 2025, we had 91 employees, eight of whom held M.D.
degrees and 32 of whom held Ph.D.
15 unchanged sentences
Our corporate headquarters are located at 1200 Avenue of the Americas, Suite 200, New York, New York 10036.
−Removed: We also have an office at Lochhamer Schlag 21, 82166 Graefelfing, Germany and a research laboratory in Planegg, Germany.
+Added: We also have an office at Lochhamer Schlag 21, 82166 Gräfelfing, Germany and a research laboratory in Planegg, Germany.
Our telephone number is (332) 255-9818.
3 unchanged sentences
Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.