A Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of ALD-102 Solution in Subjects With Alopecia Areata

Inclusion Criteria:

In order to be eligible to participate in this study, a subject must meet all of the following criteria, either at the screening and Day 1 visits or only at 1 of the specified visits (screening or Day 1) as noted in the criterion:

1. Male or female subject aged 18 to 55 years, inclusive, at the time of informedconsent.

2. Subject has a body mass index (BMI) between 18.0-35.0 kg/m2, inclusive, atscreening.

3. Subject has a body weight ≥ 50 kg, inclusive, at screening.

4. Subject has a clinically confirmed diagnosis of AA at screening visit, based oninvestigator's judgement.

5. For the treatment area(s) receiving ALD-102 Solution: subject must have AA lesion(s)that can accommodate the required number of injections per cohort: 20 injections forCohorts 1#-3# and 40 injections for Cohort 4#.

• A single scalp lesion of AA should preferably be selected as the treatment areato receive all injections.

• For Cohorts 1#-3#: a total of 20 injections requires a scalp treatmentarea of 12 cm2 (1.86 in2).

• For Cohort 4#: a total of 40 injections requires a scalp treatment area of 28 cm2 (4.34 in2).

• If a single scalp lesion of AA cannot accommodate the full number of requiredinjections per cohort, multiple scalp treatment areas may be selected:

• In such cases, each scalp treatment area must be large enough to accommodateat least 6 injections (2 cm2 [0.31 in2]).

• All selected treatment area(s) must display a near-complete or complete absenceof terminal hairs and should be clinically similar, as judged by theinvestigator.

6. For the control area:

• Cohorts 1# and 2#: subjects must have a control AA scalp lesion selectedmeasuring approximately 2 cm² (0.31 in2) to receive 6 placebo injections. Thisarea should be located ≥ 6 cm from the designated treatment area(s), exhibit anear-complete or complete absence of terminal hairs, be clinically similar tothe selected treatment area(s) as judged by the investigator, and preferably bepositioned contralaterally to one of the selected treatment areas.

• Cohorts 3# and 4#: subjects must have an untreated AA scalp lesion selectedmeasuring at least 2 cm² (0.31 in2). This area should be located ≥ 6 cm fromthe designated treatment areas, exhibit a near-complete or complete absence ofterminal hairs, be clinically similar to the selected treatment area(s) asjudged by the investigator, and preferably be positioned contralaterally to oneof the selected treatment areas.

7. Duration of current episode of hair loss at the treatment and control areas > 6months but < 5 years at screening and Day 1, along with investigators' assessmentthat hair regrowth is possible. Total duration of current episode of hair lossoutside of treatment and control areas and total duration since diagnosis of AAcould be > 5 years.

8. No evidence of active regrowth or hair loss present at baseline and no known historyof significant regrowth or hair loss, as per investigator's judgement, over the last 6 months.

9. Subject is willing to keep the same hairstyle and color (eg, hair products, process,and timing for hair appointments) for the duration of the trial. Note: Hair dying and shaving of scalp is allowed during the trial but not within 2weeks prior to a study visit.

10. For female subject of childbearing potential involved in any sexual intercourse thatcould lead to pregnancy: the subject must agree to use a highly effectivecontraceptive method in addition to use of condom for their non-vasectomized malepartner(s) from ≥ 4 weeks prior to Day 1 until ≥ 16 weeks after the last injection,and refrain from egg retrieval/egg donation during this period. Highly effectivecontraceptive methods include hormonal contraceptives (eg, combined oralcontraceptive, patch, vaginal ring, injectable, or implant), intrauterine devices orintrauterine systems, vasectomized partner(s) (provided his vasectomy was performed ≥ 4 months prior to Screening), tubal ligation or double barrier methods ofcontraception (eg, male condom with cervical cap, male condom with diaphragm, andmale condom with contraceptive sponge) in conjunction with spermicide. Note: Subjects must have been on a stable dose of hormonal contraceptives for ≥ 4weeks before Day 1. Note: The above list of contraceptive methods does not apply to subjects who areabstinent for ≥ 4 weeks before Day 1 and will continue to be abstinent frompenile-vaginal intercourse throughout the trial or for ≥ 16 weeks after the lastinjection. The reliability of sexual abstinence needs to be evaluated in relation tothe duration of the clinical trial and the preferred and usual lifestyle of thesubject. Periodic abstinence (calendar, symptothermal, post-ovulation methods) isnot acceptable. Note: A female subject of nonchildbearing potential is defined as follows:

• Female subject who has had surgical sterilization (hysterectomy, bilateraloophorectomy, or bilateral salpingectomy)

• Female subject who has had a cessation of menses for ≥ 12 months prior to thescreening visit without an alternative medical cause, and afollicle-stimulating hormone (FSH) test confirming nonchildbearing potential (refer to laboratory reference ranges for confirmatory levels).

11. For male subject involved in any sexual intercourse that could lead to pregnancy,subject must agree to use a condom and their female partner must use one of thehighly effective contraceptive methods listed in Inclusion Criterion #10, from Day 1until ≥ 16 weeks after the last injection and refrain from donating sperm duringthis period. If the female partner of a male subject uses any of the hormonalcontraceptive methods listed above, this contraceptive method should be used by thefemale partner from ≥ 4 weeks before Day 1 until ≥ 16 weeks after the lastinjection.

12. Female subject of childbearing potential must have a negative serum pregnancy testat screening and negative urine pregnancy test at Day 1.

13. Subject is willing to participate and is capable of giving a signed and datedinformed consent. Note: Consent must be obtained prior to any study-related procedures.

14. Subjects must be willing to comply with all study procedures and must be availablefor the duration of the study.

15. Subjects must be willing to receive approximately 20 to 40 intradermal injectionsevery 4 weeks (number of injections will vary for each cohort).

Exclusion Criteria:

A subject who meets any of the following criteria at the screening and/or Day 1 visits, as applicable, will be excluded from participation in this study:

1. Very severe AA, defined by SALT score ≥ 95 at screening and/or Day 1, includingalopecia universalis and alopecia totalis.

2. Presence of another form of alopecia (eg, androgenetic alopecia [AGA], traction andscarring alopecia, telogen effluvium). Note: Subjects with AGA are permitted only if the disorder is clinically distinct,physically separate, and does not affect or interfere with treatment or assessmentof the selected treatment and control area(s) of AA. The diagnosis of AA should beclear and unambiguous, and the pattern and location of AGA should not overlap withor compromise the evaluation of the selected treatment and control areas of AA.

3. Presence of diffuse type of AA. Note: Subjects with presence of ophiasis or siaphopatterns of AA are allowed.

4. History or presence of hair transplants.

5. History or presence of micropigmentation of the scalp. Note: microblading of theeyebrows is permitted.

6. Subject is a female who is breastfeeding, pregnant, or who is planning to becomepregnant during the study.

7. Subject is known to have immune deficiency or is immunocompromised.

8. Subject has a history of cancer or lymphoproliferative disease within 5 years priorto Day 1. Subjects with successfully treated nonmetastatic cutaneous squamous cellor basal cell carcinoma and/or localized carcinoma in situ of the cervix are not tobe excluded.

9. Subject had a major surgery within 8 weeks prior to Day 1 or has a major surgeryplanned during the study.

10. Subject has any clinically significant medical condition orphysical/laboratory/ECG/vital signs abnormality that would, in the opinion of theinvestigator, put the subject at undue risk or interfere with the interpretation oftrial results.

11. Subject has a positive result for hepatitis B virus (HBV; positive for hepatitis Bsurface antigens [HBsAg] or positive for hepatitis B antibodies to core antigens [anti-HBc]; subjects having a negative HBsAg and a positive anti-HBc may enroll ifthey have a positive hepatitis B surface antibody [anti-HBs] demonstrating naturalimmunity), hepatitis C virus (HCV; positive for HCV antibodies; however, a subjectwith documented proof of cure from HCV may be enrolled), or human immunodeficiencyvirus (HIV).

12. Subject has a current or recent clinically serious viral, bacterial, fungal, orparasitic infection, including but not limited to the following:

13. History of systemic infection requiring hospitalization, parenteralantimicrobial therapy, or as otherwise judged clinically significant by theinvestigator within 6 months prior to Day 1;

14. Have active chronic or acute skin infection requiring treatment with systemicantibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks prior to Day 1, or superficial skin infections within 1 week prior toDay 1;

15. History (single episode) of disseminated herpes zoster or disseminated herpessimplex, or a recurrent (more than one episode of) localized, dermatomal herpeszoster;

16. Known active tuberculosis (TB) or a positive TB infection test at screening.Subject will be evaluated for latent TB infection with a purified proteinderivative (PPD) test or a QuantiFERONTB Gold test. Subjects who demonstrateevidence of latent TB infection (either PPD ≥ 5 mm of induration or positiveQuantiFERON-TB Gold test, irrespective of Bacillus Calmette-Guérin vaccinationstatus) will only be allowed to participate in the study if there is documentedevidence of a completed adequate treatment course for latent TB (with negativechest x-ray findings for active TB). Note: A recent viral upper respiratory tract infection or uncomplicated urinarytract infection should not be considered clinically serious.

17. At screening, any of the following (tests may be repeated once within the samescreening period to confirm results prior to Day 1):

18. Absolute neutrophil count < 1.5 x 109/L;

19. Absolute lymphocyte count < 0.5 x 109/L;

20. Hemoglobin < 11.0 g/dL or hematocrit < 30%;

21. Platelet count < 100 x 109/L;

22. Clinically significant abnormal estimated creatinine clearance as perinvestigator judgement (eg, < 90 mL/min based on the Chronic Kidney DiseaseEpidemiology Collaboration [CKD-EPI] formula) or serum creatinine value > 1.5times the upper limit of normal (ULN);

23. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2 x theULN;

24. Total bilirubin ≥ 1.5 x ULN; subjects with a history of Gilbert's syndrome mayhave a direct bilirubin measured and would be eligible for this study providedthe direct bilirubin is ≤ ULN.

25. Subject has a history of clinically significant heart disease in the opinion of theinvestigator (eg, cardiomyopathy, major congenital heart disease,Wolff-Parkinson-White syndrome, heart attack, stroke, or blood clots).

26. Subject is currently receiving anti-coagulants or medications known to causethrombocytopenia (unless considered safe by the investigator to stop and washout forthe duration of the study).

27. Active forms of other inflammatory skin disease(s) or evidence of other skinconditions on the scalp (eg, psoriasis, seborrheic dermatitis, lupus) at screeningand/or Day 1, that in the opinion of the investigator might interfere withevaluation of hair regrowth.

28. Subject has presence of any tattoos, scratches, open sores, or skin damages in thetarget treatment or control areas that, in the opinion of the investigator, mayinterfere with study evaluations.

29. Subject is currently treated or was treated within 4 weeks prior to Day 1 with anysystemic treatment or oral medication for inflammatory condition that in the opinionof the investigator might interfere with the safety or efficacy assessments; shorthalf-life medications like ibuprofen, paracetamol, and antihistamines areacceptable.

30. Subject is currently receiving a nonbiological investigational product or device orhas received one within 4 weeks prior to Day 1.

31. Subject has received a live or live-attenuated vaccine within 4 weeks prior to Day 1or plans to receive a live or live-attenuated vaccine during the study and up to 4weeks or 5 half-lives (of the study product), whichever is longer, after the laststudy product administration.

32. Use of systemic and/or intralesional steroids within 8 weeks of Day 1 visit. Note:Intranasal and inhaled corticosteroids are allowed. Eye and ear drops containingcorticosteroids are also allowed.

33. Use of systemic treatments including, but not limited to, anthralin, squaric acid,diphenylcycloprophenone (DPCP), dinitrochlorobenzene (DCNB), tacrolimus, minoxidil,or any other medication which in the opinion of the investigator may affect hairregrowth within 4 weeks of Day 1 visit.

34. Subject has received any ultraviolet (UV)-B phototherapy (including tanning beds),has had psoralen-UV-A (PUVA) treatment, or excimer laser within 4 weeks prior to Day

36. Topical medicated treatment on the scalp that could affect AA including, but notlimited to, topical corticosteroids, calcineurin inhibitors, minoxidil, JAKinhibitors, medical devices within 2 weeks prior to Day 1 visit. Note: Topical medicated treatments are permitted outside of the scalp.

37. Subject has previously used a systemic JAK inhibitor for their AA (eg. baricitinib,ritlecitinib, deuruxolitinib) and discontinued for lack of efficacy (informationobtained from medical chart or subject's physician, or directly from the subject). Note: Subjects that used a systemic JAK inhibitor for AA and discontinued foranother reason than lack of efficacy, or used a systemic JAK inhibitor for anotherreason than AA, are allowed but must have discontinued the systemic JAK inhibitor atleast 6 months prior to Day 1.

38. Use of platelet-rich plasma injections in the last 12 weeks prior to Day 1.

39. Subject has received any marketed or investigational biological agent within 12weeks or 5 half-lives (whichever is longer) prior to Day 1.

40. Subject who has had previous treatment with any biologic B-cell-depleting therapy (eg, rituximab, ocrelizumab, or ofatumumab) or other B-cell targeting therapy (eg,belimumab) within 12 months before Day 1.

41. Subject who has received previous treatment with pDC inhibiting therapies (eg, antiimmunoglobulin-like transcript [ILT]7, anti-blood dendritic cell antigen 2 [BDCA2]).

42. Subject has received any prescription products containing exogenous androgens,including but not limited to testosterone, or anabolic-androgenic steroids, withinthe past 6 months before Day 1. Note: There is no washout period for over-the-counter (OTC), supplements, and/orherbal product that can contain exogenous androgens or can affect hair regrowth.However, if the subject is using any of these products for the purpose of AA, theymust stop using the products at the time of informed consent and for the duration ofthe trial.

43. Subject has a known or suspected allergy to ALD-102 or any component of theinvestigational product.

44. Subject has a known history of clinically significant drug or alcohol abuse in thelast year prior to Day 1.

45. Subject has a history of an allergic reaction or significant sensitivity tolidocaine or other local anesthetics.

46. Subject has a history of hypertrophic scarring or keloid formation in scars orsuture sites.

47. Subject has taken anticoagulant medication, such as heparin, low molecular weight (LMW)-heparin, warfarin, antiplatelets (except low-dose aspirin ≤ 81 mg which willbe allowed), within 2 weeks prior to Day 1, or has a contraindication to skinbiopsies. Short half-life nonsteroidal anti-inflammatory drugs (NSAIDs) will not beconsidered antiplatelets and will be allowed.

48. Subject is not able to tolerate intradermal injection or has a known sensitivity toneedle injection.

49. Subject is institutionalized because of legal or regulatory order.